75 research outputs found
FrĂŒherkennung von Dysphagien bei Parkinson (IPS)
Kontext: Dysphagien stellen bei Parkinson-Syndromen einen negativen prognostischen PrĂ€diktor fĂŒr die verbleibende Ăberlebenszeit dar. Sie fĂŒhren zu Aspirationen, Aspirationspneumonien, Malnutrition und Dehydration und schrĂ€nken die LebensqualitĂ€t der Patienten massiv ein. Die aktuelle Studienlage weist darauf hin, dass die durchschnittliche Ăberlebensdauer von Parkinson-Patienten mit manifester Dysphagie bei ein bis zwei Jahren liegt und (Aspirations-) Pneumonien eine der hĂ€ufigsten Todesursachen sind.
Problem: Dysphagien werden in der Regel zu spĂ€t erkannt und eine entsprechende Therapie beginnt zumeist erst bei massiveren Schluckstörungen mit GesundheitsschĂ€den. StandardmĂ€Ăige Schluckdiagnostiken zur Profilaxe werden bislang nicht durchgefĂŒhrt und ausreichend valide Screening-Tools, wie etwa Patientenfragebögen zur Evaluierung von Schluckstörungen bei Parkinson-Patienten, fehlen in der klinischen Praxis.
Beitrag: Diese Dissertation stellt den 26-Item-umfassenden MĂŒnchener Dysphagie Test â Parkinsonâs Disease (MDT-PD) vor, ein Screeningverfahren in Form eines klinischen Patientenfragebogens zur FrĂŒherkennung von Schluckstörungen und ihrer Graduierung bei idiopathischem Parkinson-Syndrom (IPS) einschlieĂlich einer bedienerfreundlichen Web- Applikation zur schnellen und örtlich flexiblen Auswertung (BetriebssystemunterstĂŒtzung: Windows, Mac OS, iOS, Android u.a.). Daneben werden zwei Befundungsbögen zur standardisierten klinischen und videoendoskopischen Schluck-Diagnostik vorgestellt, welche klar definierte, ordinale Symptom-Rating-Skalen beinhalten.
Methoden/ Validation: Der innerhalb drei Phasen und einem Pre-Test entwickelte Fragebogen wurde in einer Studie mit 82 IPS-Probanden unter Ausschluss von vordiagnostizierter Schluckstörung, Demenz oder chronischer Depression evaluiert (m=46, w=36; Ă Alter ± Standardabweichung: 70,9 J. ± 8,7 J.; Ă Erkrankungsdauer nach Erstdiagnose: 11,0 J. ± 6,3 J.; Ă H&Y: 3,3; Ă UPDRS III: 29,5 P. ± 13,3 P.). Als Vergleichsparameter kamen die neu konzipierten Symptomschweregradskalen innerhalb der standardisierten klinischen sowie videoendoskopischen Dysphagie-Diagnostik zum Einsatz. Die klinische Untersuchung bestand aus einem Ruhe-, Reflex- und FunktionsprĂŒfungs-Part sowie einer Schluckproben-Testung; bei der instrumentellen Diagnostik wurde sich an das FEESÂź-Protokoll angelehnt, welches parkinsonspezifisch weiterentwickelt wurde: Neben der Erhebung funktioneller Parameter wurde sowohl die Gefahr fĂŒr/ der Grad der laryngealen Penetration/ Aspiration innerhalb der Schlucktestung abgebildet als auch beginnende Dysphagie-Symptomatiken wie posteriores Bolus-Leaking und pharyngeale Residuen sowie Speichel-Akkumulation berĂŒcksichtigt und graduell unterschieden. In der klinischen sowie videoendoskopischen Diagnostik (DurchfĂŒhrungen im On-drug-state) wurde die Nahrungsaufnahme mit folgenden Konsistenzen, quantitativ deckungsgleich und in alltagsrelevanter Menge, geprĂŒft: dĂŒnnflĂŒssig (90 ml Wasser, blau eingefĂ€rbt), fest (1â2 Scheibe Mischbrot mit Rinde und Aufstrich, â8x7x1cm) und trocken/ bröselig (1 Keks, Ă 5cm) sowie die Einnahme von zwei Tabletten (teilbare ProLiveVita-Fit-Blocktablette, â19x8x7 mm; Placebo-Hepa-Lichtenstein, Ă 8mm).
Ergebnisse: Der MDT-PD erfĂŒllt die TestgĂŒtekriterien der klassischen Testtheorie. Durch die Receiver-Operating-Characteristics (ROC)-Analyse wurden zwei Cut-Offs fĂŒr die GruppengröĂen nicht auffĂ€llig vs. auffĂ€llig (3,65) und nicht auffĂ€llig vs. aspirationsgefĂ€hrdet (4,79) ermittelt. Die DiskriminierungsgĂŒte des (nach den Regressions-Koeffizienten) gewichteten MDT-PD-Summenscores ergibt fĂŒr die Dysphagie-Einteilungen a) unauffĂ€llig vs. auffĂ€llig eine SensitivitĂ€t (Sens) von 82% sowie eine SpezifitĂ€t (Spez) von 71% (Kreuzvalidierung: Sens 82%/ Spez 62%/ Cut-off 3,62) und b) nicht auffĂ€llig vs. aspirationsgefĂ€hrdet eine SensitivitĂ€t von 90% sowie eine SpezifitĂ€t von 86% (Kreuzvalidierung: Sens 90%/ Spez 81%/ Cut-off 4,75). FĂŒr den Zusammenhang zwischen dem Kriterien-Summenscore und dem gewichteten MDT-PD-Summenscore konnte in den Studiendaten eine starke Korrelation mit einem Spearman-Rho Korrelationskoeffizienten von +0,699 (p<0,001) beobachtet werden. FĂŒr die Fragebogen-Items des MDT-PD wurde ein Cronbachs-Alpha von 0,913 berechnet, welches auf eine sehr hohe interne Konsistenz hinweist.
Die standardisierten Diagnostikbögen (klinisch/ endoskopisch) können Dysphagiologen zur Anwendung und Praxistauglichkeits-PrĂŒfung bereit gestellt werden, welche die Test- HauptgĂŒtekriterien der ObjektivitĂ€t und der Skalierbarkeit, in Teiltestungen der ValiditĂ€t und ReliabilitĂ€t sowie die NebengĂŒtekriterien erfĂŒllen; die Validierung des Gesamt-Diagnostik- Inventars stellt eine Zukunftsarbeit dar; die Interrater-ReliabilitĂ€tsprĂŒfung des endoskopischen Befundbogens wurde bereits begonnen.
In den Nebenanalysen ergaben sich moderate positive Korrelationen zwischen Dysphagie und einem höheren Hoehn und Yahr-Grad (Kendall-Tau-b= +0,430 mit p<0,001) sowie einem mittelgradigen UPDRS-III-Wert (p=0,01, Spearman-Rho= +0,479 mit p<0,001); keine statistisch signifikanten Assoziationen ergaben sich fĂŒr: niedrigen BMI, lĂ€ngere Erkrankungsdauer, Dysarthrophonie und Patientenalter; klinisch relevante Tendenzen in Richtung Dysphagie-Bestehen zeigten sich aber hinsichtlich: verringerter Boluskontrolle, höherem drooling score scale-Wert, kognitiver BeeintrĂ€chtigung, schwerer Dysarthrophonie und BMI unterhalb der Altersuntergrenze.
Konklusion: Ărzten und Therapeuten wird mit dem MDT-PD ein valides, reliables und praxistaugliches Screening-Tool zur prĂ€ventiven Dysphagie-RisikoabschĂ€tzung sowie Graduierung (nicht auffĂ€llig, auffĂ€llig, aspirationsgefĂ€hrdet) von Dysphagien bei IPS- Patienten zur VerfĂŒgung gestellt; mit der additionalen Auswertungsoption der Web- Applikation (www.mdt-parkinson.de) soll die Implementierung des MDT-PD in den klinischen Alltag vereinfacht werden. Dem Diagnoseergebnis entsprechend, kann eine weiterfĂŒhrende, apparative Schluckdiagnostik sowie ein frĂŒher Behandlungsbeginn zur Erhaltung der LebensqualitĂ€t und zur Verhinderung gesundheitsgefĂ€hrdender Konsequenzen eingeleitet werden. Die Ăbertragbarkeit auf atypische Parkinson-Syndrome muss noch untersucht werden
Developing a Sense of Knowing and Acquiring the Skills to Manage Pain in Children with Profound Cognitive Impairments: Mothers' Perspectives
Children with profound cognitive impairment (PCI) are a heterogenous group who often experience frequent and persistent pain. Those people closest to the child are key to assessing their pain. This mixed method study aimed to explore how parents acquire knowledge and skills in assessing and managing their child's pain. Eight mothers completed a weekly pain diary and were interviewed at weeks 1 and 8. Qualitative data were analysed using thematic analysis and the quantitative data using descriptive statistics. Mothers talked of learning through a system of trial and error ("learning to get on with it"); this was accomplished through "learning to know without a rule book or guide"; "learning to be a convincing advocate"; and "learning to endure and to get things right." Experiential and reflective learning was evident in the way the mothers developed a "sense of knowing" their child's pain. They drew on embodied knowledge of how their child usually expressed and responded to pain to help make pain-related decisions. Health professionals need to support mothers/parents to develop their knowledge and skills and to gain confidence in pain assessment and they should recognise and act on the mothers' concerns
Navigating Uncertainty: Health Professionals' Knowledge, Skill and Confidence in Assessing and Managing Pain in Children with Profound Cognitive Impairment
There is limited evidence to underpin the assessment and management of pain in children with profound cognitive impairment and these children are vulnerable to poor pain assessment and management. Health professionals working with children with profound cognitive impairment from a single paediatric tertiary referral centre in England were interviewed to explore how they develop and acquire knowledge and skills to assess and manage pain in children with cognitive impairment. The interviews were transcribed and subjected to thematic analysis. Nineteen health professionals representing different professional groups and different levels of experience participated in the study. A metatheme ânavigating uncertainty; deficits in knowledge and skillsâ and two core themes âframing as different and teasing things outâ and âthe settling and unsettling presence of parentsâ were identified. Uncertainty about aspects of assessing and managing the pain of children with cognitive impairment tended to erode professional confidence and many discussed deficits in their skill and knowledge set. Uncertainty was managed through engaging with other health professionals and the childâs parents. Most health professionals stated they would welcome more education and training although many felt that this input should be clinical and not classroom oriented
Multilingual Validation of the First French Version of Munich Dysphagia Test-Parkinson's Disease (MDT-PD) in the Luxembourg Parkinson's Study
The Munich Dysphagia Test for Parkinson's disease (MDT-PD) was initially developed and validated in the German population as a highly sensitive and specific self-reported screening questionnaire to detect early oropharyngeal symptoms and aspiration risk in patients with idiopathic Parkinson's disease (iPD). In order to make this tool accessible for prevention in the French speaking populations worldwide, we performed the first French translation and provide a linguistic and psychometric validation in the unique multilingual environment of the Luxembourg Parkinson's Study
Correlation between Pathologic Complete Response in the Breast and Absence of Axillary Lymph Node Metastases after Neoadjuvant Systemic Therapy
Objective:The aim was to investigate whether pathologic complete response (PCR) in the breast is correlated with absence of axillary lymph node metastases at final pathology (ypN0) in patients treated with neoadjuvant systemic therapy (NST) for different breast cancer subtypes.Background:Pathologic complete response rates have improved on account of more effective systemic treatment regimens. Promising results in feasibility trials with percutaneous image-guided tissue sampling for the identification of breast PCR after NST raise the question whether breast surgery is a redundant procedure. Thereby, the need for axillary surgery should be reconsidered as well.Methods:Patients diagnosed with cT1-3N0-1 breast cancer and treated with NST, followed by surgery between 2010 and 2016, were selected from the Netherlands Cancer Registry. Patients were compared according to the pa
Efficient Nuclear Transport of Structurally Disturbed Cargo: Mutations in a Cargo Protein Switch Its Cognate Karyopherin
The Karyopherin (Kap) family of nuclear transport receptors enables trafficking of proteins to and from the nucleus in a precise, regulated manner. Individual members function in overlapping pathways, while simultaneously being very specific for their main cargoes. The details of this apparent contradiction and rules governing pathway preference remain to be further elucidated. S. cerevisiae Lhp1 is an abundant protein that functions as an RNA chaperone in a variety of biologically important processes. It localizes almost exclusively to the nucleus and is imported by Kap108. We show that mutation of 3 of the 275 residues in Lhp1 alters its import pathway to a Kap121-dependent process. This mutant does not retain wild-type function and is bound by several chaperones. We propose that Kap121 also acts as a chaperone, one that can act as a genetic buffer by transporting mutated proteins to the nucleus
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A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia
Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL)1â3, but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p
loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia
Life and living in advanced age: a cohort study in New Zealand - Te PuÄwaitanga o Nga Tapuwae Kia Ora Tonu, LiLACS NZ: Study protocol
The number of people of advanced age (85 years and older) is increasing and health systems may be challenged by increasing health-related needs. Recent overseas evidence suggests relatively high levels of wellbeing in this group, however little is known about people of advanced age, particularly the indigenous MÄori, in Aotearoa, New Zealand. This paper outlines the methods of the study Life and Living in Advanced Age: A Cohort Study in New Zealand. The study aimed to establish predictors of successful advanced ageing and understand the relative importance of health, frailty, cultural, social & economic factors to successful ageing for MÄori and non-MÄori in New Zealand
Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers
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