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Effectiveness of educational interventions in general practice for improving medication appropriateness and deprescribing in older adults: a systematic review protocol
No full textIntroduction: Polypharmacy in older adults is a growing concern, particularly in general practice (GP), where general practitioners (GPs) are the main prescribers managing complex multimorbidity. While often necessary, polypharmacy increases the risk of potentially inappropriate prescribing (PIP), adverse drug events, hospitalisations and reduced quality of life. Although clinical medication reviews using specific tools are frequently employed to address these risks and guide a safe deprescribing process, the specific role and effectiveness of educational interventions—as a component of prescribers’ behavioural change—remain inconsistently evaluated. The objective of this review is to identify, describe and evaluate educational interventions targeting GPs, aimed at improving medication appropriateness and promoting deprescribing in older adults with polypharmacy in GP settings.
Methods and analysis: This systematic review protocol follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocols guidelines. Eligible study designs include randomised controlled trials (RCTs), cluster RCTs and quasi-experimental studies. Studies must target GPs, GP trainees or primary care physicians and report outcomes related to medication appropriateness, measured using validated tools (eg, Medication Appropriateness Index, Screening Tool of Older Person’s Prescriptions/Screening Tool to Alert to Right Treatment). Secondary outcomes include hospital admissions, quality of life, prescribing behaviour, medication-related harms and cost-effectiveness. In addition to evaluating effectiveness, we will characterise heterogeneity in educational content and objectives, duration/intensity, theoretical or pedagogical underpinnings, delivery format, implementation fidelity and contextual factors. A comprehensive search will be conducted in MEDLINE, EMBASE, CINAHL and CENTRAL without language or date restrictions. The systematic review will follow PRISMA 2020 guidelines for data synthesis, and if meta-analysis is not feasible, Synthesis Without Meta-analysis reporting guidelines will be used.
Ethics and dissemination: Findings will be disseminated through peer-reviewed publications and conference presentations. Results will inform the design of future educational strategies to optimise medication review and deprescribing practices in general practice and primary care, by identifying which approaches most effectively improve patient-centred outcomes and clarifying the role of educational components within complex, multicomponent interventions
Stability of individual differences in executive functions in kindergarten children – a microgenetic study
No full textExecutive functions (EF) are higher cognitive processes which are involved in new, complex tasks. EF are often subdivided into three components: updating of working memory representations, shifting between tasks or task rules, and inhibiting predominant reactions or interfering stimuli. Individual differences in EF are often used to predict academic performance. Although the temporal stability of a construct is a necessary condition for its use as a predictor, the stability of EF in children remains unclear. The present study aims to investigate the short-term stability of individual EF performance in N = 57 kindergarten children. They were tested eight times every 2–3 days with an n-back task to measure updating, a colour/shape sorting task to measure shifting, and a go/no-go task to measure inhibition. Four-week stabilities were high for inhibition and low to moderate for updating and shifting. In latent state-trait analyses, half of the variance in inhibition but very small amounts of variance in updating and shifting variance were explained by trait. Moderate to high amounts of variance in all three tasks were explained by state. The results are discussed in terms of the usefulness of the tasks for measuring stable EF in kindergarten age and for predicting later performance
Analytical fidelity calculations for photonic linear cluster state generation
No full textBy precisely timed optical excitation of their spin, optical emitters such as semiconductor quantum dots or atoms can be harnessed as sources of linear photonic cluster states. This significantly reduces the required resource overhead to reach fault-tolerant optical quantum computing. Here, we develop an algorithm that analytically tracks the global density matrix through the process of the protocol for generating linear-cluster states by Lindner and Rudolph. From this we derive a model to calculate the entangling gate fidelity and the state fidelity of the generated linear optical cluster states. Our model factors in various sources of error, such as spin decoherence and the finite excited state lifetime. Additionally, we highlight the presence of partial reinitialization of spin coherence with each photon emission, eliminating the hard limitation of coherence time. Our framework provides valuable insight into the cost-to-improvement trade-offs for device design parameters as well as the identification of optimal working points. For a combined state-of-the-art quantum dot with a spin coherence time of T2∗=535ns and an excited state lifetime of τ=23ps, we show that a near-unity entangling gate fidelity as well as near-unity state fidelity for 3-photon and 7-photon linear cluster states can be reached
Exploring the boundaries between neoplastic and reactive lymphoproliferations: lymphoid neoplasms with indolent behavior and clonal lymphoproliferations—a report of the 2024 EA4HP/SH lymphoma workshop
No full textThe boundaries between neoplastic and reactive lymphoproliferations were discussed during the 2024 European Association for Haematopathology/Society for Hematopathology workshop in Dubrovnik, Croatia. Session 5 focused on indolent lymphoid neoplasms and clonal lymphoproliferations. Seventy-two cases were submitted, representing good examples of indolent lymphomas and lymphoproliferative disorders (LPD) and their diagnostic challenges. The morphologic spectrum of primary cutaneous marginal zone lymphoma/lymphoproliferation (PC-MZL/PC-MZLPD) was discussed. PC-MZL/PC-MZLPD is divided in the immunoglobulin heavy chain switched-type and non-switched-type with some clinicopathological differences. The overlapping features between PC-MZL/PC-MZLPD and PC-CD4 + T-cell LPD were highlighted. The criteria for the diagnosis of indolent T-lymphoblastic proliferation (iT-LBP) were reviewed. Indolent T-cell lymphoproliferation of the gastrointestinal tract (iT-LPD-GI) is a rare clonal, non-destructive, and non-epitheliotropic T-cell LPD occurring in adults with a male predominance. The cases submitted to the workshop revealed clinicopathological heterogeneity. Unusual features like infiltration of the complete intestinal wall, mesenteric lymph node involvement, and splenomegaly were observed. A novel group of PD1 + /CD4 + indolent cases with intestinal tropism and dissemination to blood, bone marrow, lymph node, and skin was identified. Other indolent clonal B- and T-cell LPDs were discussed including transient, clonal CD8 + T-cell proliferations, usually the result of immune-mediated cytotoxic T-cell response to virus or neoantigens, and the recently described follicle center lymphoma (FLC) of the lower female genital tract. The increasing awareness of the existence of indolent LPDs should avoid unnecessary treatments. In this report, novel findings, recommendations for diagnosis, open questions, and diagnostic challenges raised by the cases submitted to the workshop will be discussed
Severe late-onset neutropenia after rituximab administration
No full textRituximab (RTX) bewirkt durch Bindung an das CD20-Antigen eine B‑Zell-Depletion. Eine weniger bekannte unerwünschte Arzneimittelwirkung von RTX ist die ca. 6 Monate nach Therapiebeginn auftretende Late-onset-Neutropenie (LON). Als klinisches Management sollten unter RTX-Therapie regelmäßige Differenzialblutbildkontrollen erfolgen. Bei akuten LON-Episoden kann neben einer Watch-and-Wait-Strategie eine unterstützende Gabe von G‑CSF („granulocyte colony-stimulating factor“) diskutiert werden. Die Reexposition mit RTX nach stattgehabter LON wird nach Abwägung von Risikofaktoren und ausführlicher Aufklärung im Allgemeinen als vertretbar erachtet. In dieser Fallserie möchten wir 2 Fälle von rheumatologischen Patienten mit schwerwiegender LON nach RTX-Gabe vorstellen.Rituximab (RTX) causes B‑cell depletion by binding to the CD20 antigen. A less well-known adverse drug reaction of RTX is late-onset neutropenia (LON), which occurs approximately 6 months after treatment initiation. As clinical management, regular differential blood cell counts should be performed during RTX treatment. Besides a watch-and-wait strategy, supportive administration of granulocyte colony-stimulating factor (G-CSF) can be discussed for acute LON episodes. Re-exposure to RTX after LON has occurred is generally considered acceptable after diligent benefit-risk evaluation and thorough patient information. In this case series, we would like to present 2 cases of rheumatology patients with severe LON after RTX administration
Distress screening in patients with high-grade glioma: diagnostic accuracy in relation to a structured clinical interview in a multicenter cluster-randomized controlled trial
No full textPurpose
Structured clinical interviews, such as the Structured Clinical Interview for DSM (SCID), are considered the gold standard for diagnosing mental disorders but are challenging in routine clinical use due to their length. Therefore, screening instruments to identify the need for further assessment are required. The National Comprehensive Cancer Network Distress Thermometer (DT) screens for psychological distress, while the Emotional Functioning (EF) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) assesses emotional functioning. Both are frequently used in clinical routine. Additionally, three brief screening questions (TSQ), specifically developed for patients with glioma and integrated into doctor–patient consultations, may also be used for screening. This study aimed to evaluate the ability of the three tools to identify patients with psychiatric comorbidities as diagnosed by the SCID.
Methods
Using data from glioma patients treated at 13 German hospitals participating in a cluster-randomized trial, discriminative abilities were assessed using receiver operating characteristic (ROC) curves and corresponding areas under the curve (AUCs). Confidence intervals (CIs) were estimated, and hypothesis tests were conducted using bootstrapping.
Results
Of the 691 patients interviewed, 31% presented with at least one mental disorder. The EF scale demonstrated the best discriminative ability (AUC 0.70, 95% CI: 0.66–0.74), followed by the DT (AUC 0.69, 95% CI: 0.62–0.76), and the TSQ total score (AUC 0.61, 95% CI: 0.55–0.66).
Conclusion
While all three tools performed better than random chance, none demonstrated convincing discriminative ability in identifying psychiatric comorbidities. In practice, screening tools can identify a substantial proportion of patients with mental disorders, however at the cost of a considerable number of false negatives
The effect of the education system on the gender gaps in mathematics and reading competencies
No full textTo date, gender inequalities persist and vary across countries, e.g., the gender gap in mathematics and reading competencies, indicating that education system characteristics affect gender inequalities. Education inequalities lead to inequalities in living standards and expectations over the life-course, e.g., health, income, and social participation. Therefore, my aim is to explain how education system characteristics affect the gender gaps in mathematics and reading competencies of 15-year-old students.
To explain the effects of education system characteristics on gender inequalities in competencies, I adapt the macro-meso-micro model. At the micro level, I use gender-specific socialization theory, highlighting how gender-specific expectations and stereotypes cause gendered interests and skills and therefore gender differences in mathematics and reading. Deriving a macro-micro link, I explain how education system characteristics, i.e., differentiation, standardization, competition, school time, evaluation and accountability, and compulsory education, could increase or decrease the gender-specific socialization effects, leading to larger or smaller gender gaps in mathematics and reading competencies.
Based on this theoretical framework, I perform a cross-national comparison of 78 countries participating in the Programme for International Student Assessment (PISA) 2018, combined with further researched macro data. Using three-level mixed-effects models, I include cross-level interactions for all education system characteristics with gender to test the derived hypotheses. The results indicate that the considered education system characteristics affect the gender gaps in mathematics and reading competencies to varying degrees. In particular, competition, school time, evaluation and accountability, and compulsory education explain the gender gaps
Loss of synaptic Munc13-1 underlies neurotransmission abnormalities in spinal muscular atrophy
No full textSpinal muscular atrophy (SMA) is a devastating neurodegenerative disease characterized by degeneration of spinal motoneurons, leading to muscle atrophy and synaptic loss. SMN functions in mRNA splicing, transport, and local translation are crucial for maintaining synaptic integrity. Within the presynaptic membrane, the active zone orchestrates the docking and priming of synaptic vesicles. The Munc13 family proteins are key active zone components that operate precise neurotransmitter release in conjunction with voltage-gated Ca2+ channels (VGCCs). However, the role of Munc13s in synaptic dysfunction in SMA remains elusive. Our findings reveal that Munc13-1 loss, but not Munc13-2, is closely linked to synaptic aberrations in SMA. Specifically, Munc13-1 mRNA localization in axons is dependent on Smn, and its disruption leads to impaired AZ assembly and VGCC clustering in motoneurons, ultimately reducing neuronal activity. In contrast, Munc13-2 does not appear to be essential for AZ assembly or motoneuron differentiation, as its functions can be compensated by Munc13-1. These findings highlight the pivotal role of Munc13-1 in synapse integrity and point to potential therapeutic targets for mitigating synaptic loss in SMA
Discordance between patient and physician reported global disease activity in PsA is associated with mental health—a cross-sectional analysis
No full textPsoriatic arthritis (PsA) is a complex disease with heterogeneous disease manifestations. Composite scores including patient reported parameters are the recommended tools to measure these different aspects. Patient and physician often show discordance in their disease assessment. To describe the discordance between patient (PtGA) and physician reported global disease activity (PhGA) and to show its association with mental health. Descriptive cross-sectional analysis of three independent cohorts of PsA patients – RABBIT-SpA register, national database (NDB), RheumaDatenRheport GbR (RHADAR) network – receiving routine rheumatology care in Germany. Association between depressive symptoms and discordance between PtGA and PhGA was analysed using a linear regression model taking age, sex, and depression score into account. 1931 RABBIT-SpA, 1794 NDB, and 1728 RHADAR patients were analysed. Mean age was 55, 56, and 60 years. Mean discordance (PtGA-PhGA) was 1.8 in RABBIT-SPA, 1.9 in NDB, and 2 in RHADAR. Discordance > = 3 was present in 34% (RABBIT-SpA), 35% (NDB), and 37% (RHADAR). Discordance increased with increasing PtGA. In patients with severe depressive symptoms, discordance was larger than in those with no depressive symptoms. Depressive symptoms were significantly associated with discordance also if age and sex were accounted for. In this analysis of three independent PsA cohorts, we found a clinically meaningful discordance between physician and patient assessed disease activity in more than a third of the patients. As patients report higher levels of disease activity, discordant judgments become increasingly prevalent. Depressive symptoms are strongly associated with discordant assessments of global disease activity
Investigation of clinical and laboratory factors influencing treatment response and the course of palliative systemic therapy in recurrent or metastatic head and neck cancer
No full textDie vorliegende Studie analysierte Daten von insgesamt 153 Patienten mit rezidivierten und/oder metastasierten Kopf-Hals-Tumoren. Rund 86 % der Patienten waren männlich, das durchschnittliche Alter zum Zeitpunkt der Diagnosestellung betrug 63 Jahre und die Mehrheit der Patienten wies ein Normalgewicht auf. Am häufigsten wurden Hypopharynxkarzinome diagnostiziert, gefolgt von Tumoren der Mundhöhle und des Oropharynx. Das Vorliegen von Fernmetastasen stellte den häufigsten Grund für den Beginn einer palliativen Systemtherapie dar. Die Untersuchung ausgewählter klinischer Parameter (Alter, Geschlecht, BMI, Art des Rezidivs, Tumorlokalisation) hinsichtlich ihres potenziellen prognostischen Einflusses auf das Überleben ergab keine eindeutige
Korrelation zwischen diesen Parametern und dem Überleben der Patienten. Auch wenn
sich diese Ergebnisse in der Literatur wiederfinden, gibt es Studien, die insbesondere die Rezidivart als auch die Tumorlokalisation als signifikante Prognosemarker identifizieren konnten. In Anbetracht der analysierten laborchemischen Faktoren, haben Patienten mit einem physiologischen GGT-Wert 6,6 g/dl als auch einem Hämatokrit-Wert > 32 %, ein besseres Gesamt- und progressionsfreies Überleben erzielt als Patienten mit abnormen Laborwerten. Hierbei sind sowohl übereinstimmende als auch abweichende Ergebnisse in der existierenden Literatur vorzufinden. Daher lassen sich sowohl die untersuchten klinischen als auch laborchemischen Parameter nicht als verlässliche Prognosemarker heranziehen. Angesichts der begrenzten Studienlage zu prognostischen Blutwerten besteht hier Bedarf an weiteren Untersuchungen, um verlässlichere Vorhersagen zu ermöglichen. Der Einfluss der erhaltenen Systemtherapie auf das Überleben wurde ebenfalls analysiert. Die drei untersuchten Therapieformen umfassten „Docetaxel mono“, „Platin plus Docetaxel“ und „Platin plus 5-Fluoruracil“. Obwohl die „Platin plus Docetaxel“- Gruppe ein signifikant längeres progressionsfreies Überleben im Vergleich zu den anderen Therapiegruppen erzielte, zeigte keine dieser Therapieoptionen eine signifikant bessere Gesamtüberlebensrate. Dies deckt sich mit zahlreichen anderen Studien. Fortschritte im Gesamtüberleben wurden erst 2008 mit der Einführung des EXRTREME- Regimes und 2019 durch den Einsatz von Immuncheckpoint-Inhibitoren erreicht. In vorliegender Arbeit wurden jedoch nur zwei Patienten nach dem EXTREME-Protokoll und 15 Patienten in der Erstlinientherapie mit Immuntherapeutika behandelt. Dies könnte zum einen am überwiegend unzureichenden Performance-Status des Patientenkollektivs für das EXTREME-Schema liegen, zum anderen daran, dass während des Untersuchungszeitraums von 2012 bis 2020 noch zu wenige Patienten mit Immuntherapien behandelt wurden. Die Wirksamkeit von Immuntherapien und ihr Potenzial als neuer Goldstandard wird daher in zukünftigen Studien weiter überprüft werden. Im letzten Teil der Analyse wurde der Einfluss der Anzahl erhaltener Therapielinien auf das Gesamt- und progressionsfreie Überleben untersucht. Es zeigte sich ein signifikanter Gesamtüberlebensvorteil für Patienten, die mehr als eine Therapielinie erhielten, was auch andere Studien bestärken. Insbesondere Patienten mit Fernmetastasen sowie Patienten unter 70 Jahren profitierten von mehreren Therapielinien hinsichtlich des Gesamtüberlebens. Vor Einleitung einer palliativen Anbindung sollte daher, sofern es der Allgemeinzustand des Patienten zulässt, eine weitere Therapielinie in Erwägung gezogen werden.This study analyzed data from a total of 153 patients with recurrent and/or metastatic head and neck tumors. Approximately 86% of the patients were male, the average age at the time of diagnosis was 63 years, and the majority of patients were of normal weight. Hypopharyngeal carcinomas were the most commonly diagnosed tumors, followed by tumors of the oral cavity and oropharynx. The presence of distant metastases was the most common reason for initiating palliative systemic therapy. The examination of selected clinical parameters (age, gender, BMI, type of recurrence, tumor location) with regard to their potential prognostic influence on survival did not reveal any clear correlation between these parameters and patient survival. Although
these results are reflected in the literature, there are studies that have identified the type of recurrence and tumor location in particular as significant prognostic markers. Considering the laboratory chemical factors analyzed, patients with a physiological GGT value 6.6 g/dl, and a hematocrit value > 32% achieved better overall and progression-free survival than patients with abnormal laboratory values. Both consistent and divergent results can be found in the existing literature. Therefore, neither the clinical nor the laboratory parameters examined can be used as reliable prognostic markers. Given the limited number of studies on prognostic blood values, further research is needed to enable more reliable predictions. The influence of systemic therapy on survival was also analyzed. The three forms of therapy examined were “docetaxel mono,” “platinum plus docetaxel,” and “platinum plus 5-fluorouracil.” Although the “platinum plus docetaxel” group achieved significantly longer progression-free survival compared to the other therapy groups, none of these therapy options showed a significantly better overall survival rate. This is consistent with numerous other studies.Progress in overall survival was not achieved until 2008 with the introduction of the EXTREME regimen and in 2019 with the use of immune checkpoint inhibitors. In the present study, however, only two patients were treated according to the EXTREME protocol and 15 patients received first-line therapy with immunotherapeutics. This could be due, on the one hand, to the predominantly inadequate performance status of the patient cohort for the EXTREME regimen and, on the other hand, to the fact that too few patients were treated with immunotherapies during the study period from 2012 to 2020. The efficacy of immunotherapies and their potential as a new gold standard will therefore be further investigated in future studies. The last part of the analysis examined the influence of the number of treatment lines received on overall and progression-free survival. A significant overall survival benefit was observed for patients who received more than one line of treatment, which is also confirmed by other studies. In particular, patients with distant metastases and patients under the age of 70 benefited from multiple lines of therapy in terms of overall survival. Before initiating palliative care, therefore, a further line of therapy should be considered, provided that the patient's general condition allows it