Preanalytics: online-training for medical assistants – international study on demand, benefit and sustainability

Hintergrund: Bei Laboruntersuchungen entstehen die meisten Fehler in der präanalytischen Phase. Im ambulanten Bereich sind Medizinische Fachangestellte (MFA) für die Gewinnung und Handhabung von Proben zuständig. Methoden: In einer internationalen Kohortenstudie prüften wir die Fragen 1. Wie viele Medizinische Fachangestellte (MFA, Deutschland) und Praxisassistentinnen (MPA, Schweiz) lassen sich für eine Fortbildung gewinnen? 2. Wie ist ihr Kenntnisstand von Präanalytik? und die Hypothese: Mit einer Online-Fortbildung kann ein signifikanter akuter und nachhaltiger Wissenszuwachs erreicht werden. Dazu wurde MFA und MPA eine kostenlose „Online-Fortbildung Präanalytik bei Blut- und Probeentnahmen“ angeboten. Sie umfasste drei Tests (T1–T3) mit Single- und Multiple Choice Fragen und eine Lerneinheit zwischen T1 und T2. Alle Tests enthielten dieselben Fragen. T3 fand drei Monate nach T2 statt. Bei 60% richtigen Antworten in T3 wurde ein Zertifikat vergeben. Ergebnisse: Es registrierten sich 332 Personen für die Fortbildung, 262 nahmen teil, 199 Datensätze waren statistisch auswertbar. In T1 erzielten 54,7% der TeilnehmerInnen 60% richtige Antworten, in T 2 waren es 94,97% und drei Monate später in T3 92,45%. Schlussfolgerung: Die Kenntnisse von MFA und MPA zur Präanalytik scheinen unzureichend zu sein. Nur 0,15% der Angesprochenen haben an der Qualifizierung teilgenommen. Die Online-Fortbildung konnte einen nachhaltigen Wissenszuwachs zur Präanalytik vermitteln

Multimodale Schulung von Hausärzten - Evaluation und Wissenszuwachs im Rahmen der Initiative Demenzversorgung in der Allgemeinmedizin (IDA).

In many industrialized countries diagnostic and therapeutic deficits in the management of patients with dementia are well documented. Due to demographic trends the next years will see a further rise in the number of affected patients. Accordingly, the knowledge and competence of the physicians taking care of these patients need to be keep up-to-date. In the context of the three-armed cluster-randomized IDA trial (IDA = "Initiative Demenzversorgung in der Allgemeinmedizin"; Dementia Management Initiative in General Medicine), general practitioners (GPs) from the trial area (Bavaria, Germany) were trained in the diagnosis and treatment of dementia. METHODS: The educational training concept was based on the evidence-based guideline of Witten/Herdecke University (UWH). All participating GPs (n = 137, January 2006) received three hours training in the diagnosis of dementia. In addition, a subgroup was trained for two hours in dementia therapy (n = 90). Both groups obtained information about the study design. The didactic concept included screen and oral presentations by opinion leaders, video and interactive elements. At the beginning of the training sessions participants had to fill in a pilot-tested questionnaire with 20 multiple choice questions addressing the diagnosis and therapy of dementia (pretest). The same questionnaire was completed at the end of the training session (posttest) complemented by an evaluation sheet. Overall and intergroup differences between pre- and post-test results (increase in knowledge) were compared using the Chi-Square test. RESULTS: Overall, the quality of the training received a positive rating by the participants. By the end of January 2006, 137 doctors had been trained. The mean knowledge gain was 4.0+2.6 correctly answered questions (p<0.001; Cl 3.6 to 4.5) comparing pre- and posttest (n = 132). In the group trained on diagnosis alone (n = 45), the gain averaged 2.0+/-1.9 questions. The group with additional training on therapy (n = 87) achieved a difference of 5.1 -2.3 questions (p<0.001). DISCUSSION: Participants of the dementia training achieved a substantial gain of knowledge. The extent of this knowledge increase was associated with the attendance to respective training modules. An ongoing trial will add further information about knowledge translation in the field of dementia

Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors

Under endoplasmic reticulum (ER) stress, unfolded proteins accumulate in the ER to activate the ER transmembrane kinase/endoribonuclease (RNase)—IRE1α. IRE1α oligomerizes, autophosphorylates, and initiates splicing of XBP1 mRNA, thus triggering the unfolded protein response (UPR). Here we show that IRE1α’s kinase-controlled RNase can be regulated in two distinct modes with kinase inhibitors: one class of ligands occupy IRE1α’s kinase ATP-binding site to activate RNase-mediated XBP1 mRNA splicing even without upstream ER stress, while a second class can inhibit the RNase through the same ATP-binding site, even under ER stress. Thus, alternative kinase conformations stabilized by distinct classes of ATP-competitive inhibitors can cause allosteric switching of IRE1α’s RNase—either on or off. As dysregulation of the UPR has been implicated in a variety of cell degenerative and neoplastic disorders, small molecule control over IRE1α should advance efforts to understand the UPR’s role in pathophysiology and to develop drugs for ER stress-related diseases

Allosteric Inhibition of the IRE1α RNase Preserves Cell Viability and Function during Endoplasmic Reticulum Stress

Depending on endoplasmic reticulum (ER) stress levels, the ER transmembrane multidomain protein IRE1α promotes either adaptation or apoptosis. Unfolded ER proteins cause IRE1α lumenal domain homo-oligomerization, inducing trans autophosphorylation that further drives homo-oligomerization of its cytosolic kinase/endoribonuclease (RNase) domains to activate mRNA splicing of adaptive XBP1 transcription factor. However, under high/chronic ER stress, IRE1α surpasses an oligomerization threshold that expands RNase substrate repertoire to many ER-localized mRNAs, leading to apoptosis. To modulate these effects, we developed ATP-competitive IRE1α Kinase-Inhibiting RNase Attenuators-KIRAs-that allosterically inhibit IRE1α's RNase by breaking oligomers. One optimized KIRA, KIRA6, inhibits IRE1α in vivo and promotes cell survival under ER stress. Intravitreally, KIRA6 preserves photoreceptor functional viability in rat models of ER stress-induced retinal degeneration. Systemically, KIRA6 preserves pancreatic β cells, increases insulin, and reduces hyperglycemia in Akita diabetic mice. Thus, IRE1α powerfully controls cell fate but can itself be controlled with small molecules to reduce cell degeneration

Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors

Under endoplasmic reticulum (ER) stress, unfolded proteins accumulate in the ER to activate the ER transmembrane kinase/endoribonuclease (RNase)—IRE1α. IRE1α oligomerizes, autophosphorylates, and initiates splicing of XBP1 mRNA, thus triggering the unfolded protein response (UPR). Here we show that IRE1α’s kinase-controlled RNase can be regulated in two distinct modes with kinase inhibitors: one class of ligands occupy IRE1α’s kinase ATP-binding site to activate RNase-mediated XBP1 mRNA splicing even without upstream ER stress, while a second class can inhibit the RNase through the same ATP-binding site, even under ER stress. Thus, alternative kinase conformations stabilized by distinct classes of ATP-competitive inhibitors can cause allosteric switching of IRE1α’s RNase—either on or off. As dysregulation of the UPR has been implicated in a variety of cell degenerative and neoplastic disorders, small molecule control over IRE1α should advance efforts to understand the UPR’s role in pathophysiology and to develop drugs for ER stress-related diseases