Treatment as required versus regular monthly treatment in the management of neovascular age-related macular degeneration: a systematic review and meta-analysis

Background: To investigate whether treatment as required ‘pro re nata’ (PRN) versus regular monthly treatment regimens lead to differences in outcomes in neovascular age-related macular degeneration (nAMD). Regular monthly administration of vascular endothelial growth factor (VEGF) inhibitors is an established gold standard treatment, but this approach is costly. Replacement of monthly by PRN treatment can only be justified if there is no difference in patient relevant outcomes. Methods: Systematic review and meta-analysis. The intervention was PRN treatment and the comparator was monthly treatment with VEGF-inhibitors. Four bibliographic databases were searched for randomised controlled trials comparing both treatment regimens directly (head-to-head studies). The last literature search was conducted in December 2014. Risk of bias assessment was performed after the Cochrane Handbook for Systematic Reviews of Interventions. Findings: We included 3 head-to-head studies (6 reports) involving more than 2000 patients. After 2 years, the weighted mean difference in best corrected visual acuity (BCVA) was 1.9 (95% CI 0.5 to 3.3) ETDRS letters in favour of monthly treatment. Systemic adverse events were higher in PRN treated patients, but these differences were not statistically significant. After 2 years, the total number of intravitreal injections required by the patients in the PRN arms were 8.4 (95% CI 7.9 to 8.9) fewer than those having monthly treatment. The studies were considered to have a moderate risk of bias. Conclusions: PRN treatment resulted in minor but statistically significant decrease in mean BCVA which may not be clinically meaningful. There is a small increase in risk of systemic adverse events for PRN treated patients. Overall, the results indicate that an individualized treatment approach with anti-VEGF using visual acuity and OCT-guided re-treatment criteria may be appropriate for most patients with nAMD

Living systematic review and meta-analysis of the prostate MRI diagnostic test with Prostate Imaging Reporting and Data System (PI-RADS) assessment for the detection of prostate cancer:study protocol

INTRODUCTION: The Prostate Imaging Reporting and Data System (PI-RADS) standardises reporting of prostate MRI for the detection of clinically significant prostate cancer. We provide the protocol of a planned living systematic review and meta-analysis for (1) diagnostic accuracy (sensitivity and specificity), (2) cancer detection rates of assessment categories and (3) inter-reader agreement. METHODS AND ANALYSIS: Retrospective and prospective studies reporting on at least one of the outcomes of interest are included. Each step that requires literature evaluation and data extraction is performed by two independent reviewers. Since PI-RADS is intended as a living document itself, a 12-month update cycle of the systematic review and meta-analysis is planned. This protocol is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Protocols statement. The search strategies including databases, study eligibility criteria, index and reference test definitions, outcome definitions and data analysis processes are detailed. A full list of extracted data items is provided. Summary estimates of sensitivity and specificity (for PI-RADS ≥3 and PI-RADS ≥4 considered positive) are derived with bivariate binomial models. Summary estimates of cancer detection rates are calculated with random intercept logistic regression models for single proportions. Summary estimates of inter-reader agreement are derived with random effects models. ETHICS AND DISSEMINATION: No original patient data are collected, ethical review board approval, therefore, is not necessary. Results are published in peer-reviewed, open-access scientific journals. We make the collected data accessible as supplemental material to guarantee transparency of results. PROSPERO REGISTRATION NUMBER: CRD42022343931

Health-related preferences of older patients with multimorbidity: the protocol for an evidence map

Introduction: Interaction of conditions and treatments, complicated care needs and substantial treatment burden make patient–physician encounters involving multimorbid older patients highly complex. To optimally integrate patients’ preferences, define and prioritise realistic treatment goals and individualise care, a patient-centred approach is recommended. However, the preferences of older patients, who are especially vulnerable and frequently multimorbid, have not been systematically investigated with regard to their health status. The purpose of this evidence map is to explore current research addressing health-related preferences of older patients with multimorbidity, and to identify the knowledge clusters and research gaps. Methods and analysis: To identify relevant research, we will conduct searches in the electronic databases MEDLINE, EMBASE, PsycINFO, PSYNDEX, CINAHL, Social Science Citation Index, Social Science Citation Index Expanded and the Cochrane library from their inception. We will check reference lists of relevant articles and carry out cited reference research (forward citation tracking). Two independent reviewers will screen titles and abstracts, check full texts for eligibility and extract the data. Any disagreement will be resolved and consensus reached with the help of a third reviewer. We will include both qualitative and quantitative studies, and address preferences from the patients’ perspectives in a multimorbid population of 60 years or older. There will be no restrictions on the publication language. Data extraction tables will present study and patient characteristics, aim of study, methods used to identify preferences and outcomes (ie, type of preferences). We will summarise the data using tables and figures (ie, bubble plot) to present the research landscape and to describe clusters and gaps. Ethics and dissemination: Due to the nature of the proposed evidence map, ethics approval will not be required. Results from our research will be disseminated by means of specifically prepared materials for patients, at relevant (inter)national conferences and via publication in peer-reviewed journals

Age-related differences in integrin expression in peripheral blood lymphocytes

Alpha integrins play an important role in cell to cell and cell to extra-cellular matrix interactions required for an effective T-lymphocyte-mediated immune response, however little is known about age related differences in expression of alpha integrins on T-cells in humans. We here measured alpha-4 (α4) integrin (CD49d) expression on T-lymphocytes via peripheral blood sampling, comparing parameters between cohorts of young and old adults. No age-related differences were found for the absolute numbers of T-cells, although the percentage of CD4+ T-cells in older adults was significantly greater and the percentage of CD8+ T-cells lower than in younger cohorts. Percentage and absolute numbers of CD3+ T-cells co-expressing CD49d were significantly lower in older adults compared to younger cohorts, and the percentage of gated CD4+ and CD8+ cells that co-labelled positively for CD49d was also reduced in this group. There were no age-related differences in circulating levels of cytokines (Type I interferons) that are known to regulate cell surface integrin expression. Reduced expression of alpha integrins on T-cells may be an early indicator of the loss of homeostatic control that occurs with ageing, contributing to diminished effector T-cell responses during senescence

Inter-professional Service Learning to Increase Students\u27 Understanding of Migrant Latino Health

Learning Objectives At the end of this seminar participants will be able to: 1.Explain the relevance of inter-professional, cultural competent, global health approaches to health assessment and interventions at home and abroad. 2.Identify evidence-based programs to improve target population health, utilizing the CLAS standards to advance health equity, improve quality and help eliminate health disparities. 3.Design a service learning inter-professional health education course with teaching strategies for cultural competency training that utilizes academic and clinical partnerships

Extent of non-publication in cohorts of studies approved by research ethics committees or included in trial registries

BACKGROUND: The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries. METHODS AND FINDINGS: Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%-52.4%, I2 = 94.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%-65.9%, I2 = 98.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2-3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6-2.5). The probability of publication within two years after study completion ranged from 7% to 30%. CONCLUSIONS: A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased

Effectiveness of screening preschool children for amblyopia: a systematic review

<p>Abstract</p> <p>Background</p> <p>Amblyopia and amblyogenic factors like strabismus and refractive errors are the most common vision disorders in children. Although different studies suggest that preschool vision screening is associated with a reduced prevalence rate of amblyopia, the value of these programmes is the subject of a continuing scientific and health policy discussion. Therefore, this systematic review focuses on the question of whether screening for amblyopia in children up to the age of six years leads to better vision outcomes.</p> <p>Methods</p> <p>Ten bibliographic databases were searched for randomised controlled trials, non-randomised controlled trials and cohort studies with no limitations to a specific year of publication and language. The searches were supplemented by handsearching the bibliographies of included studies and reviews to identify articles not captured through our main search strategy.</p> <p>Results</p> <p>Five studies met the inclusion criteria. Of these, three studies suggested that screening is associated with an absolute reduction in the prevalence of amblyopia between 0.9% and 1.6% (relative reduction: between 45% and 62%). However, the studies showed weaknesses, limiting the validity and reliability of their findings. The main limitation was that studies with significant results considered only a proportion of the originally recruited children in their analysis. On the other hand, retrospective sample size calculation indicated that the power based on the cohort size was not sufficient to detect small changes between the groups. Outcome parameters such as quality of life or adverse effects of screening have not been adequately investigated in the literature currently available.</p> <p>Conclusion</p> <p>Population based preschool vision screening programmes cannot be sufficiently assessed by the literature currently available. However, it is most likely that the present systematic review contains the most detailed description of the main limitations in current available literature evaluating these programmes. Therefore, future research work should be guided by the findings of this publication.</p

Research response to coronavirus disease 2019 needed better coordination and collaboration: a living mapping of registered trials

Objectives: Researchers worldwide are actively engaging in research activities to search for preventive and therapeutic interventions against coronavirus disease 2019 (COVID-19). Our aim was to describe the planning of randomized controlled trials (RCTs) in terms of timing related to the course of the COVID-19 epidemic and research question evaluated. Study Design and Setting: We performed a living mapping of RCTs registered in the WHO International Clinical Trials Registry Platform. We systematically search the platform every week for all RCTs evaluating preventive interventions and treatments for COVID-19 and created a publicly available interactive mapping tool at https://covid-nma.com to visualize all trials registered. Results: By August 12, 2020, 1,568 trials for COVID-19 were registered worldwide. Overall, the median ([Q1–Q3]; range) delay between the first case recorded in each country and the first RCT registered was 47 days ([33–67]; 15–163). For the 9 countries with the highest number of trials registered, most trials were registered after the peak of the epidemic (from 100% trials in Italy to 38% in the United States). Most trials evaluated treatments (1,333 trials; 85%); only 223 (14%) evaluated preventive strategies and 12 postacute period intervention. A total of 254 trials were planned to assess different regimens of hydroxychloroquine with an expected sample size of 110,883 patients. Conclusion: This living mapping analysis showed that COVID-19 trials have relatively small sample size with certain redundancy in research questions. Most trials were registered when the first peak of the pandemic has passed

Augenwachstum, Optik und räumliches Sehen bei der Maus, einem neuen Säugetiermodell für die Myopieforschung

1. The mouse has a number of advantages over other animal models to study myopia, including the availability of knock-out models, the extensive knowledge on its genome, transcriptome and proteom, and its physiology. However, no data are published on the development of its ocular biometry and optical properties. Therefore, a paraxial schematic model of the growing eye for the most common laboratory mouse strain, the C57BL/6 mouse, for the age range between 22 and 100 days, was developed (Schmucker & Schaeffel, 2004a). 2. Until now, a major drawback of the mouse was that its ocular dimensions cannot be measured in vivo, and that the current techniques post-mortem suffer from limited resolution. Therefore, the potential of a new technique, optical low coherence interferometry, adapted for short measurement distances by Meditec, Carl Zeiss, Jena, Germany, was tested. Using this technique, ocular biometry was performed in mice with normal vision and after deprivation of form vision (Schmucker & Schaeffel, 2004b). 3. Despite the evidence that mice have some spatial vision, it is not known at present at which illuminances it is important. Therefore, spatial acuity of wild-type C57BL6/J mice was measured in a newly developed automated optomotor paradigm at different illuminances. Furthermore, mutant mice lacking either rods or cones, or both, were studied to determine the rod and cone contribution to spatial vision (Schmucker, Seeliger, Humphries, Biel, & Schaeffel, 2005). 4. To determine how diffusers, spectacle lenses and atropine affect spatial vision in the mouse, the contrast thresholds at different spatial frequencies with lenses or diffusers, or after topical application of eye drops with atropine were determined. These information are necessary to find out which treatments could effectively induce refractive errors in young animals. Measurements were performed under both photopic conditions and in dim light, using an optomotor paradigm that was developed in the course of the study (see 3.) (Schmucker & Schaeffel, 2005). Referenzen: 1. Schmucker, C., & Schaeffel, F. (2004a). A paraxial schematic eye model for the growing C57BL/6 mouse. Vision Research, 44(16), 1857-1867. 2. Schmucker, C., & Schaeffel, F. (2004b). In vivo biometry in the mouse eye with low coherence interferometry. Vision Research, 44(21), 2445-2456. 3. Schmucker, C., Seeliger, M., Humphries, P., Biel, M., & Schaeffel, F. (2005). Grating acuity at different luminances in wild-type mice and in mice lacking cone or rod function. Investigative Ophthalmology & Visual Science, 46(1), 398-407. 4. Schmucker, C., & Schaeffel, F. (2005). Contrast sensitivity of wild-type mice wearing diffusers or spectacle lenses, and the effect of atropine. Vision Research, in press (online publication 1st July 2005).1. Die Maus ist ein vielversprechendes Modell in der Myopieforschung, da das Genom vollständig sequenziert ist, viele transgene Modelle und Inzuchtstämme zur Verfügung stehen und Selektionszüchtung leicht möglich ist. Um das Auge der Maus jedoch einsetzen zu können, ist eine detaillierte Beschreibung der Optik in der Ontogenese erforderlich. Im Rahmen dieser Arbeit wurde deshalb ein schematisches Modell für das wachsende Auge von Wildtypmäusen (C57BL/6) entwickelt (Schmucker & Schaeffel, 2004a). 2. Die Erzeugung und Messung von Kurzsichtigkeit stellt im Mausauge (3 mm lang) eine besondere Herausforderung dar. Zur Messung der Achsenlänge in vivo wurde eine neu entwickelte Technik, die optische Niederkohärenz-Interferometrie ("ACMaster", Carl Zeiss, Jena) getestet. Damit ist es gelungen, die Achsenlänge des Mausauges mit einer Standardabweichung von 10 mikrometer zu bestimmen. Ausserdem konnte damit gezeigt werden, dass das Mausauge, wie auch die Augen anderer Tiermodelle, auf Störung der retinalen Bildqualität mit beschleunigtem Längenwachstum reagiert (Schmucker & Schaeffel, 2004b). 3. Obwohl man bereits weiss, dass Mäuse eine geringe Sehschärfe aufweisen (ca. 0.50 Zyklen/Grad), ist nichts darüber bekannt, bei welchen Helligkeiten die Tiere am besten sehen. Um das Sehsystem bei Mäusen genauer zu untersuchen, wurde ein automatisiertes Optomotorik-Verfahren entwickelt. Damit war es möglich, die Sehschärfe bei Wildtypmäusen bei unterschiedlichen Helligkeiten zu untersuchen. Ausserdem wurden Mausmutanten untersucht, denen Stäbchen und/oder Zapfen fehlten. Überraschenderweise, sahen Mäuse besser bei heller Beleuchtung, und dies hauptsächlich mit den Stäbchen, nicht mit den Zapfen (Schmucker, Seeliger, Humphries, Biel, & Schaeffel, 2005). 4. Um herauszufinden, inwieweit Mattgläser, Brillengläser (bis ±20 dpt) und Atropin Augentropfen Einfluss auf die Sehschärfe von Mäusen haben, wurden die Kontrastschwellen mit Hilfe des Optomotorik-Verfahrens (siehe 3.) bestimmt. Die Untersuchungen wurden bei unterschiedlichen Ortsfrequenzen sowohl im photopischen als auch im skotopischen Bereich durchgeführt. Diese Messungen gaben Aufschluss darüber, durch welche Behandlungsmethoden am effektivsten Refraktionsfehler im Mausauge erzeugt werden können (Schmucker & Schaeffel, 2005). Referenzen: 1. Schmucker, C., & Schaeffel, F. (2004a). A paraxial schematic eye model for the growing C57BL/6 mouse. Vision Research, 44(16), 1857-1867. 2. Schmucker, C., & Schaeffel, F. (2004b). In vivo biometry in the mouse eye with low coherence interferometry. Vision Research, 44(21), 2445-2456. 3. Schmucker, C., Seeliger, M., Humphries, P., Biel, M., & Schaeffel, F. (2005). Grating acuity at different luminances in wild-type mice and in mice lacking cone or rod function. Investigative Ophthalmology & Visual Science, 46(1), 398-407. 4. Schmucker, C., & Schaeffel, F. (2005). Contrast sensitivity of wild-type mice wearing diffusers or spectacle lenses, and the effect of atropine. Vision Research, in press (online Veröffentlichung am 1. Juli 2005)