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

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

Systematic review finds that study data not published in full text articles have unclear impact on meta-analyses results in medical research.

A meta-analysis as part of a systematic review aims to provide a thorough, comprehensive and unbiased statistical summary of data from the literature. However, relevant study results could be missing from a meta-analysis because of selective publication and inadequate dissemination. If missing outcome data differ systematically from published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention effect. As part of the EU-funded OPEN project (www.open-project.eu) we conducted a systematic review that assessed whether the inclusion of data that were not published at all and/or published only in the grey literature influences pooled effect estimates in meta-analyses and leads to different interpretation. Systematic review of published literature (methodological research projects). Four bibliographic databases were searched up to February 2016 without restriction of publication year or language. Methodological research projects were considered eligible for inclusion if they reviewed a cohort of meta-analyses which (i) compared pooled effect estimates of meta-analyses of health care interventions according to publication status of data or (ii) examined whether the inclusion of unpublished or grey literature data impacts the result of a meta-analysis. Seven methodological research projects including 187 meta-analyses comparing pooled treatment effect estimates according to different publication status were identified. Two research projects showed that published data showed larger pooled treatment effects in favour of the intervention than unpublished or grey literature data (Ratio of ORs 1.15, 95% CI 1.04-1.28 and 1.34, 95% CI 1.09-1.66). In the remaining research projects pooled effect estimates and/or overall findings were not significantly changed by the inclusion of unpublished and/or grey literature data. The precision of the pooled estimate was increased with narrower 95% confidence interval. Although we may anticipate that systematic reviews and meta-analyses not including unpublished or grey literature study results are likely to overestimate the treatment effects, current empirical research shows that this is only the case in a minority of reviews. Therefore, currently, a meta-analyst should particularly consider time, effort and costs when adding such data to their analysis. Future research is needed to identify which reviews may benefit most from including unpublished or grey data

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

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

Mental burden and its risk and protective factors during the early phase of the SARS-CoV-2 pandemic: systematic review and meta-analyses

BACKGROUND Mental burden due to the SARS-CoV-2 pandemic has been widely reported for the general public and specific risk groups like healthcare workers and different patient populations. We aimed to assess its impact on mental health during the early phase by comparing pandemic with prepandemic data and to identify potential risk and protective factors. METHODS For this systematic review and meta-analyses, we systematically searched PubMed, PsycINFO, and Web of Science from January 1, 2019 to May 29, 2020, and screened reference lists of included studies. In addition, we searched PubMed and PsycINFO for prepandemic comparative data. Survey studies assessing mental burden by the SARS-CoV-2 pandemic in the general population, healthcare workers, or any patients (eg, COVID-19 patients), with a broad range of eligible mental health outcomes, and matching studies evaluating prepandemic comparative data in the same population (if available) were included. We used multilevel meta-analyses for main, subgroup, and sensitivity analyses, focusing on (perceived) stress, symptoms of anxiety and depression, and sleep-related symptoms as primary outcomes. RESULTS Of 2429 records retrieved, 104 were included in the review (n = 208,261 participants), 43 in the meta-analysis (n = 71,613 participants). While symptoms of anxiety (standardized mean difference SMD 0.40; 95{\%} CI 0.15-0.65) and depression (SMD 0.67; 95{\%} CI 0.07-1.27) were increased in the general population during the early phase of the pandemic compared with prepandemic conditions, mental burden was not increased in patients as well as healthcare workers, irrespective of COVID-19 patient contact. Specific outcome measures (eg, Patient Health Questionnaire) and older comparative data (published $\geq$5 years ago) were associated with increased mental burden. Across the three population groups, existing mental disorders, female sex, and concerns about getting infected were repeatedly reported as risk factors, while older age, a good economic situation, and education were protective. CONCLUSIONS This meta-analysis paints a more differentiated picture of the mental health consequences in pandemic situations than previous reviews. High-quality, representative surveys, high granular longitudinal studies, and more research on protective factors are required to better understand the psychological impacts of the SARS-CoV-2 pandemic and to help design effective preventive measures and interventions that are tailored to the needs of specific population groups

Flow diagram outlining the screening and selection process of articles.

<p>Flow diagram outlining the screening and selection process of articles.</p

Mean decrease in central foveal thickness (CFT) from baseline in μm.

<p>Mean decrease in central foveal thickness (CFT) from baseline in μm.</p