Conducting a vaccine trial in a low- and middle-income country (LMIC) can present unique challenges and lessons learned. This Ebola vaccine trial, enrolling 699 healthcare providers and frontliners ...and jointly set up by the University of Antwerp (Sponsor) and the University of Kinshasa (Principal Investigator (PI)), was conducted in Boende, a remote city in the Democratic Republic of the Congo (DRC), between December 2019 and October 2022 (ClinicalTrials.gov: NCT04186000). While being bound by strict ICH-GCP and international funder regulations, this trial, exemplary for being a public-private partnership, required collaboration between several international stakeholders (e.g., two universities, a pharmaceutical company, and a clinical research organization), local communities and government agencies. Here we address several logistical and administrative challenges, cultural differences, language barriers and regulatory, political, and ethical considerations over the trial's 2.5-year duration, while tailoring and adapting the study to the specific local context. Lessons learned include the importance of clear communication with participants in all phases of the study, but also within the study team and among different stakeholders. Challenges, mitigations, and lessons learned are presented in nine categories (e.g., safety management; trial documentation, tools, and materials; communication, staff training and community engagement/sensitization; financial and administrative hurdles; and more). Ultimately, to reach the successful end of the vaccine trial in this remote Ebola endemic area in the DRC, careful planning, collaboration, and great flexibility and adaptability was often required from all involved partners. Despite the encountered challenges, the vaccine trial discussed in this paper was able to obtain high participant retention rates (i.e., 92% of participants completed the study). We hope that other international teams aspiring to conduct similar trials in remote areas of LMICs can learn from the way our challenges were addressed, mitigations developed, and lessons were learned.
To describe recurrence patterns and investigate candidate risk factors for recurrences of central serous chorioretinopathy.
In 46 patients with acute central serous chorioretinopathy and follow-up ...>12 months after first episode resolution, parameters influencing recurrences were retrospectively evaluated using a frailty Cox proportional hazard survival model. Covariates included baseline systemic findings: age, gender, corticosteroid use, stress, shift work, sleep disorder, depression, allergy, cardiovascular risk; baseline optical coherence tomography findings: subfoveal choroidal thickness, pigment epithelial detachment pattern (regular/bump/irregular), number of subretinal hyperreflective foci at leakage site; baseline angiographic findings: fluorescein leakage intensity (intense/moderate/subtle/absent), hyperpermeability pattern on indocyanine-green angiography (focal/multifocal); and episode-related findings: duration and treatment of previous episode.
Twenty of 46 subjects (43%) presented ≥1 recurrences during a mean follow-up of 29.9 ± 9.5 months (range, 15-54 months). Follow-up duration did not differ between cases with or without recurrences (P = 0.3). Worse final visual acuity levels (logarithm of the minimal angle of resolution) were associated with a higher number of episodes during follow-up (P = 0.032, r = 0.28). In a univariate analysis, higher subfoveal choroidal thickness (P = 0.021), nonintense fluorescein leakage (= moderate/subtle/absent, P = 0.033), multiple subretinal hyperreflective foci (P = 0.026), and shift work (P < 0.0001) were significantly associated with recurrences, with a near-significant influence of irregular pigment epithelial detachment (P = 0.093). In a multivariate analysis, higher subfoveal choroidal thickness (P = 0.007), nonintense fluorescein leakage (P = 0.003) and shift work (P < 0.0001) remained significant and independent risk factors for recurrences.
Multiple factors influence the risk of central serous chorioretinopathy recurrence. These findings may contribute to identify patients at higher risk, who could benefit from earlier or more intensive treatment.
Abstract
While attention dysregulation is a promising early indicator of neurodevelopmental risk, in particular attention‐deficit/hyperactivity disorder (ADHD), it is difficult to characterize ...clinical concern due to its developmental expectability at the transition to toddlerhood. Thus, explicating the typical:atypical continuum of risk indicators is among the key future directions for research to promote early identification and intervention, and prevent decrements in the attainment of developmental milestones into early childhood. In this paper, we present the Multidimensional Assessment Profiles—Attention Regulation Infant‐Toddler (MAPS‐AR‐IT) Scale, a novel parent‐report survey of dimensional, developmentally specified indicators of attention (dys)regulation. Item Response Theory was employed to characterize the typical:atypical spectrum of both normative and more concerning dysregulation (including the contexts in which behavior occurs). We provide evidence of the validity of this measure in capturing the full typical:atypical spectrum via a longitudinal sample of typically developing children at 12–18 months of age (baseline) via concurrent scores on well‐validated temperament and clinical measures. We also examine longitudinal stability and predictive validity if the MAPS‐AR‐IT via a clinical interview of ADHD symptoms at 24–30 months (follow‐up). While not diagnostic, we present evidence of the utility of the MAPS‐AR‐IT in explicating individual neurodevelopmental risk and elucidating the broader typicality of behaviors related to attention (dys)regulation.
Resumen
Aunque la desregulación de la atención es un prometedor indicador temprano del riesgo neural de desarrollo, en particular el trastorno de déficit en la atención/hiperactividad (ADHD), es difícil caracterizar las preocupaciones clínicas debido al factor de expectativa de desarrollo al momento de la transición a la temprana niñez. De manera que explicar la progresión típica:atípica de indicadores de riesgo está entre las futuras directrices claves para la investigación con el fin de promover la temprana identificación e intervención, y prevenir disminuciones en el alcance de hitos críticos hacia la temprana niñez. En este ensayo, presentamos la Escala de Perfiles de Evaluación Multidimensional – Regulación de la Atención del Infante‐Niño Pequeñito (MAPS‐AR‐IT) una novedosa encuesta de reporte del progenitor, acerca de la (des)regulación de la atención, dimensional y específica para el desarrollo. Aportamos evidencia de la validez de esta medida para captar la completa gama típica:atípica por medio de una muestra longitudinal de niños típicamente en desarrollo, a los 12–18 meses de edad (edad base) por medio de puntajes concurrentes sobre el temperamento bien validado y las medidas clínicas, así como también la estabilidad longitudinal y la validez de predicción por medio de una entrevista clínica de síntomas de ADHD a los 24–30 meses (seguimiento). Se empleó la Teoría de Respuesta al Asunto para caracterizar la gama típica:atípica tanto de la desregulación normativa como de la más preocupante (incluyendo los contextos en los cuales ocurre el comportamiento). Aunque no se trata de diagnóstico, presentamos evidencia de la utilidad de MAPS‐AR‐IT para explicar el riesgo individual de desarrollo neural y elucidar el más amplio aspecto típico de comportamientos relacionados con la (des)regulación de la atención.
Résumé
Bien que la dysrégulation de l'attention soit un indicateur précoce prometteur du risque neurodéveloppemental, en particulier le trouble déficitaire de l'attention/hyperactivité (TDHA) il est difficile de caractériser la préoccupation clinique du fait de sa prévisibilité développementale à la transition à la petite enfance. Par conséquent, expliquer le continuum typique:atypique des indicateurs de risque s'avère être une des directions futures de recherches clé pour promouvoir l'identification et l'intervention précoce, et prévenir les baisses dans la réalisation d’étapes développementales importantes jusque dans la petite enfance. Dans cet article nous présentons l'Echelle Multidimensional Assessment Profiles – Attention Regulation Infant‐Toddler (MAPS‐AR‐IT) (échelle de profils d’évaluation multidimensionnelle – régulation de l'attention bébé‐petit enfant, abrégée selon l'anglais MAP‐AR‐IT), une étude nouvelle basée sur les rapports faits par les parents de la (dys)régulation de l'attention dimensionnelle et spécifiée selon le développement. Nous démontrons la validité de cette mesure en capturant l’éventail total typique:atypique au moyen d'un échantillon longitudinal d'enfants se développement typiquement, à 12–18 mois (ligne de case) au moyen de scores concurrents de mesures cliniques et de tempérament bien validées, ainsi qu’’une stabilité longitudinale et d'une validité prédictive au moyen d'un entretien Clinique des symptômes THHA à 24–30 mois (suivi). La Item Response Theory (IRT) a été employée pour caractériser l’éventail typique:atypique de la dysrégulation à la fois normative et celle plus inquiétante (y compris les contextes dans lesquels le comportement prend place). Bien que cela ne soit pas diagnostique, nous présentons la preuve de l'utilité de la MAPS‐AR‐IT en expliquant le risqué neurodéveloppemental individuel et en élucidant la typicalité plus large de comportements liés à la (dys)régulation de l'attention.
Zusammenfassung
Was ist typisch:atypisch bei der Aufmerksamkeitsregulation von Kleinkindern? Charakterisierung des Entwicklungsspektrums mit der Skala „Multidimensional Assessment Profiles ‐ Attention Regulation Infant‐Toddler“ (MAPS‐AR‐IT)
Aufmerksamkeitsdysregulation ist zwar ein vielversprechender Frühindikator für neurologische Entwicklungsrisiken, insbesondere für die Aufmerksamkeitsdefizit‐/Hyperaktivitätsstörung (ADHS), lässt sich aber aufgrund der Entwicklungserwartung am Übergang zum Kleinkindalter nur schwer klinisch charakterisieren. Daher gehört die Präzisierung des Kontinuums von typischen und atypischen Risikoindikatoren zu den wichtigsten künftigen Forschungsfeldern, um eine frühzeitige Erkennung und Intervention zu fördern und eine Verschlechterung des Erreichens von Entwicklungsmeilensteinen in der frühen Kindheit zu verhindern. In diesem Beitrag stellen wir die „Multidimensional Assessment Profiles ‐ Attention Regulation Infant‐Toddler (MAPS‐AR‐IT) Scale“ vor, eine neuartige Elternbefragung zur dimensionalen, entwicklungsspezifischen (Dys‐)Regulation der Aufmerksamkeit. Wir belegen die Validität dieses Maßes bei der Erfassung des gesamten typisch/atypischen Spektrums anhand einer Längsschnittstichprobe typisch entwickelter Kinder im Alter von 12–18 Monaten (Baseline) durch simultane Ergebnisse gut validierter Temperaments‐ und klinischer Maße. Die Längsschnittstabilität und prädiktive Validität belegen wir durch ein klinisches Interview zu ADHS‐Symptomen im Alter von 24–30 Monaten (Follow‐up). Die Item‐Response‐Theorie wurde eingesetzt,
um das typische bzw. atypische Spektrum sowohl der normativen als auch der eher problematischen Dysregulation (einschließlich der Kontexte, in denen das Verhalten auftritt) zu charakterisieren. Obwohl der MAPS‐AR‐IT keine diagnostische Funktion hat, zeigt er doch, dass er zur Erklärung individueller neurologischer Entwicklungsrisiken und zur Klärung der breiteren Typizität von Verhaltensweisen im Zusammenhang mit Aufmerksamkeits(dys)regulierung geeignet ist.
摘要
尽管注意力失调是神经发育风险的一个有希望的早期指标, 尤其是注意力缺陷或多动障碍 (ADHD) , 但由于其在幼儿期过渡阶段的发育预期, 很难对临床关注进行特定描述。因此, 阐明“典型:非典型”风险指标的连续性是未来研究的重要方向之一, 以促进早期识别和干预, 并防止儿童早期发育节点的实现率下降。在本文中, 我们介绍了“多维评估概要 ‐ 注意力调节幼儿 (MAPS‐AR‐IT) 量表”, 这是一种新颖的家长报告调查, 用于维度化的、发展性明确的注意力 (失调) 调节。我们采用12–18个月大 (干预前) 的典型发育儿童的纵向样本, 通过对经过充分验证的气质和临床测量同时评分, 以及通过对24–30个月大 (随访) ADHD症状的临床访谈, 提供了此测量工具在捕捉整个“典型:非典型”谱系上的有效性证据。采用“项目反应理论”来描述规范的以及更令人关注的失调 (包括行为发生的情境) 的“典型:非典型”谱系。尽管不具有诊断意义, 但我们提供了MAPS‐AR‐IT在解释个体神经发育风险, 以及阐明与注意力 (失调) 调节相关的更广泛的典型行为的实用性证据。
ملخص
ما هو النموذجي: غير المعتاد في تنظيم انتباه الأطفال الصغار؟: توصيف طيف النمو من خلال ملفات التقييم متعددة الأبعاد ‐ مقياس تنظيم انتباه الرضع والأطفال الصغار (MAPS‐AR‐IT)
ملخص
في حين أن خلل تنظيم الانتباه يعد مؤشراً مبكراً لمخاطر النمو العصبي، ولا سيما اضطراب نقص الانتباه/فرط النشاط (ADHD)، فمن الصعب وصف هذا الخطر إكلينيكياً بسبب توقعه في مرحلة النمو عند الانتقال إلى مرحلة الطفولة. وبالتالي، فإن تفسير مقياس النموذجي: غير النمطي لمؤشرات المخاطر هو من بين الاتجاهات المستقبلية الرئيسية للبحث لتعزيز التعرف والتدخل المبكر، ومنع التناقص في تحقيق مظاهر النمو في مرحلة الطفولة المبكرة. في هذا البحث، نقدم بروفايلات التقييم متعدد الأبعاد –مقياس تنظيم انتباه الرضع والأطفال الصغار (MAPS‐AR‐IT)، وهو أداة فحص جديدة لتقارير الوالدين متعددة الأبعاد حول تنظيم وعدم تنظيم الانتباه. نقدم دليلاً على صحة هذا الإجراء في تصوير الطيف النموذجي الكامل: غير النمطي عبر عينة طولية من الأطفال الذين ينمون بشكل طبيعي، في عمر 12–18 شهرًا من خلال الدرجات المتزامنة على مقاييس المزاج والمقاييس الاكلينيكية التي تم التحقق منها جيدًا، وكذلك الاستقرار الطولي والصلاحية التنبؤية من خلال مقابلة إكلينيكية لأعراض اضطراب فرط الحركة ونقص الانتباه في عمر 24–30 شهرًا (متابعة). تم استخدام نظرية الاستجابة للعنصر لوصف الطيف النموذجي: غير النمطي لانعدام التنظيم في حدوده الطبيعية وغير الطبييعية (بما في ذلك السياقات التي يحدث فيها السلوك). وعلى الرغم من أن هذا المقياس غير تشخيصي، إلا أننا نقدم دليلاً على فائدة MAPS‐AR‐IT في توضيح مخاطر النمو العصبي الفردية وتوضيح النموذجية الأوسع للسلوكيات المتعلقة بتنظيم الانتباه وعدم تنظيمه.
Medicine and architecture: a blueprint Niederberger, Craig; Zola, Zoka
Fertility and sterility,
April 2018, 2018-04-00, 20180401, Letnik:
109, Številka:
4
Journal Article
•Clinical trial regulations are becoming increasingly complex and demanding for low- and middle-income countries (LMICs)•International collaboration based on equal partnership can help LMICs perform ...high quality vaccine trials.•Maintaining acquired capacity while conducting clinical trials in LMICs is key and needs long term international support.•Transparency of lessons learned during clinical trials can assist for a more efficient conduct of trials.•This article describes the challenges, mitigations and lessons learned during the setup of a vaccine trial in a LMIC.
Since the largest Ebola outbreak in West Africa (2013–2016) highlighted the potential threat of the Ebola virus to the world, several vaccines have been under development by different pharmaceutical companies. To obtain vaccine licensure, vaccine trials assessing the safety, immunogenicity and efficacy of new vaccines among different populations (e.g. different in age, gender, race, and ethnicity) play a crucial role. However, while this deadly disease mainly affects Central and West Africa, clinical trial regulations are becoming increasingly complex and consequently more expensive, influencing the affected low- and middle-income countries (LMICs) in performing high quality clinical trials. Consequently, the completion of such trials in LMICs takes more time and vaccines and drugs take longer to be licensed. To overcome some of the obstacles faced, the EBOVAC3 consortium, funded by the European Union’s Innovative Medicines Initiative and the Coalition for Epidemic Preparedness Innovations, enabled high quality vaccine trials in Central and West Africa through extensive North-South collaborations. In this article, the encountered challenges, mitigations, recommendations and lessons learned from setting-up an Ebola vaccine trial in a remote area of the Democratic Republic of Congo are presented. These challenges are grouped into eight categories: (1) Regulatory, political and ethical, (2) Trial documents, (3) International collaborations, (4) Local trial staff, (5) Community engagement and sensitization, (6) Logistics, (7) Remoteness and climate conditions, (8) Financial. By sharing the encountered challenges, implemented mitigations and lessons learned for each of these categories, we hope to prepare and inform other researchers aspiring a well-functioning clinical trial unit in similar remote settings in LMICs. ClinicalTrials.gov identifier: NCT04186000.
•We target the worldwide coordinate-level location of Twitter users•We propose a novel Google Trends noun (GTN) spatial clustering approach•GTN only uses historical tweets and public Web data (e.g., ...Google Trends)•We collected a recent Twitter dataset with ground truth locations of 3,268 users•The best overall results were achieved by the GTN DSCAN (GTN-DB) method
User location data is valuable for diverse social media analytics. In this paper, we address the non-trivial task of estimating a worldwide city-level Twitter user location considering only historical tweets. We propose a purely unsupervised approach that is based on a synthetic geographic sampling of Google Trends (GT) city-level frequencies of tweet nouns and three clustering algorithms. The approach was validated empirically by using a recently collected dataset, with 3,268 worldwide city-level locations of Twitter users, obtaining competitive results when compared with a state-of-the-art Word Distribution (WD) user location estimation method. The best overall results were achieved by the GT noun DBSCAN (GTN-DB) method, which is computationally fast, and correctly predicts the ground truth locations of 15%, 23%, 39% and 58% of the users for tolerance distances of 250 km, 500 km, 1,000 km and 2,000 km.
After the Covid-19 pandemic, environmental rebalancing became the vital limit for humans in the third millennium. The inevitable global scenario, where perhaps accidents have crossed, can be looked ...at from another horizon, as a mosaic of local operations on the environment. The design research by the Faculty of Engineering and Architecture of the University of Cagliari, in concert with the University of Applied Arts in Vienna, and funded by the Autonomous Region of Sardinia, configures, with inland areas at its core, a fundamental perspective of the Regional Policies for a carbon-neutral Sardinia in the next 30 years.
In recent years, next to conventional rehabilitation's techniques, new technologies have been applied in stroke rehabilitation. In this context, fully immersive virtual reality (FIVR) has showed ...interesting results thanks to the level of immersion of the subject in the illusional world, with the feeling of being a real part of the virtual environment. This study aims to investigate the efficacy of FIVR in stroke rehabilitation. PubMed, Web of Science and Scopus were screened up to November 2022 to identify eligible randomized controlled trials (RCTs). Out of 4623, we included 12 RCTs involving post-acute and chronic stroke survivors, with a total of 350 patients (234 men and 115 women; mean age 58.36 years). High heterogeneity of the outcomes considered, the results showed that FIVR provides additional benefits, in comparison with standard rehabilitation. In particular, results showed an improvement in upper limb dexterity, gait performance and dynamic balance, influencing patient independence. Therefore, FIVR represents an adaptable, multi-faceted rehabilitation tool that can be considered in post-stroke rehabilitation, improving the compliance of the patients to the treatment and increasing the level of functioning and quality of life of stroke survivors.
PDF
