Visual Outcome after Intravitreal Anti-VEGF Therapy for Macular Neovascularisation Secondary to Sorsby's Fundus Dystrophy: A Systematic Review.

The aim of this paper is to summarise our own and to review published experience regarding the long-term outcome of intravitreal treatment for macular neovascularisation (MNV) secondary to Sorsby's fundus dystrophy (SFD). A systematic literature search using the MeSH terms [Sorsby] and [anti-vascular endothelial growth factor (VEGF)] was conducted in NCBI/PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ScienceDirect, Google Scholar and ClinicalTrials.gov to identify publications reporting anti-VEGF treatment outcomes in SFD. Treatment outcomes were extracted for this meta-analysis from 14 publications and an own patient reporting a total of 31 cases with a mean follow-up (FU) of 54 months. Both eyes were affected in ten (32.3%) instances. Heterogenous reporting limited the comparability of the outcomes. All papers in common, however, reported satisfied to excellent responses to anti-VEGF therapy if patients were diagnosed and treated immediately after onset of symptoms. Of 20 eyes, for which visual acuity was reported before and after treatment, five worsened and seven improved by more than 1 line, whereas eight eyes maintained their function by end of the follow up, and 11 eyes (55%) maintained a driving vision (Snellen VA ≥ 0.5). Of six eyes with a VA < 0.5, VA improved in one to VA ≥ 0.5, whereas of 14 eyes with an initial VA ≥ 0.5, this dropped to <0.5 despite therapy. In MNV secondary to SFD, the delay between first symptoms and access to anti-VEGF treatment determines subretinal scar formation and thereby, functional prognosis. If treated early, this is generally favourable under regular controls and a consequent anti-VEGF treatment of MNV activity

How are social stressors at work related to well-being and health? A systematic review and meta-analysis

Background: Social relationships are crucial for well-being and health, and considerable research has established social stressors as a risk for well-being and health. However, researchers have used many different constructs, and it is unclear if these are actually different or reflect a single overarching construct. Distinct patterns of associations with health/well-being would indicate separate constructs, similar patterns would indicate a common core construct, and remaining differences could be attributed to situational characteristics such as frequency or intensity. The current meta-analysis therefore investigated to what extent different social stressors show distinct (versus similar) patterns of associations with well-being and health. Methods: We meta-analysed 557 studies and investigated correlations between social stressors and outcomes in terms of health and well-being (e.g. burnout), attitudes (e.g. job satisfaction), and behaviour (e.g. counterproductive work behaviour). Moderator analyses were performed to determine if there were differences in associations depending on the nature of the stressor, the outcome, or both. To be included, studies had to be published in peer-reviewed journals in English or German; participants had to be employed at least 50% of a full-time equivalent (FTE). Results: The overall relation between social stressors and health/well-being was of medium size (r = -.30, p < .001). Type of social stressor and outcome category acted as moderators, with moderating effects being larger for outcomes than for stressors. The strongest effects emerged for job satisfaction, burnout, commitment, and counterproductive work behaviour. Type of stressor yielded a significant moderation, but differences in effect sizes for different stressors were rather small overall. Rather small effects were obtained for physical violence and sexual mistreatment, which is likely due to a restricted range because of rare occurrence and/or underreporting of such intense stressors. Conclusions: We propose integrating diverse social stressor constructs under the term "relational devaluation" and considering situational factors such as intensity or frequency to account for the remaining variance. Practical implications underscore the importance for supervisors to recognize relational devaluation in its many different forms and to avoid or minimize it as far as possible in order to prevent negative health-related outcomes for employees

Disease stability and extended dosing under anti-VEGF treatment of exudative age-related macular degeneration (AMD) - a meta-analysis.

PURPOSE To assess disease stability (absence of intra- and/or subretinal fluid) and the portion of eyes being capable to extend their treatment interval to ≥ 12 weeks in exudative age-related macular degeneration (AMD). METHODS A systematic literature search was performed in NCBI, PubMed, CENTRAL, and ClinicalTrials.gov to identify clinical studies reporting treatment outcomes for ranibizumab, aflibercept, and brolucizumab in exudative AMD under a treat-and-extend protocol and a follow-up of ≥ 12 months. Weighted mean differences and subgroup comparisons were used to integrate the different studies. RESULTS This meta-analysis refers to 29 published series, including 27 independent samples and 5629 patients. In the pooled group, disease stability was reported in 62.9% and 56.0%, respectively, after 12 and 24 months of treatment, whereas treatment intervals were extended to ≥ 12 weeks in 37.7% and 42.6%, respectively. Ranibizumab, aflibercept, and brolucizumab differed regarding their potential to achieve disease stability (56.3%, 64.5%, and 71.5% after 12, and 50.0%, 52.7% and 75.7% after 24 months; p = < 0.001) and to allow an interval extension to ≥ 12 weeks (28.6%, 34.2%, and 53.3% after 12, and 34.2%, 47.7%, and 41.7% after 24 months; p = < 0.001). CONCLUSION The portion of eyes achieving disease stability regressed in the second year, whereas the portion of eyes under a ≥ 12-week interval increased. This discrepancy may reflect the challenges in balancing between under-treatment and a reduced treatment burden

The Monday Effect Revisited: A Diary and Sleep Actigraphy Study

Purpose Accidents are more likely to occur during the morning hours of Mondays (Monday effect). This might be due to a higher level of cognitive failure on Monday morning at work. Methods In a pilot actigraphy study across one working week, we explored this Monday effect and regressed daily self-reported workplace cognitive failure on weekdays (Monday versus other days), background social stressors at work, delayed sleep onset and sleep duration. Diary data were gathered from 40 full-time employees. Results Confirming our assumptions, results revealed work-related cognitive failure and sleep-onset latency on the previous night to be higher on Mondays compared to other workdays. Work-related cognitive failure correlated positively with delayed sleep-onset latency and background social stressors. In multilevel regression analysis, Monday significantly explained variations in workplace cognitive failure. The addition of background social stressors at work and sleep-onset latency to the regression model showed unique contributions to the prediction of workplace cognitive failure. No significant two-way or three-way interactions between working days, sleep-onset latency or sleep duration, and background social stressors were found. Conclusion Peak levels of cognitive failure on Monday morning and the association of cognitive failure with social stressors at work contribute to understanding the mechanisms involved in the increased prevalence of occupational accidents on Monday morning. Occupational safety interventions should address both social stressors at work and individual sleep hygiene

Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus.

Diabetic retinopathy (DR) is a sight-threatening late complication of diabetes mellitus (DM). Even though its pathophysiology has not been fully elucidated, several studies suggested a role for transforming growth factor- (TGF-) β, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinase (TIMP) in the onset and progression of the disease. Consequently, the aim of this study was to analyze the concentrations of TGF-β1, TGF-β2, TGF-β3, MMP-3, MMP-9, and TIMP-1 in patients with different stages of DR in order to identify stage-specific changes in their concentrations during the progression of the disease. Serum and aqueous humor (AH) samples were collected during intraocular surgery, and eyes were classified into the following groups: healthy controls (n = 17), diabetic patients with non-apparent DR (n = 23), mild/moderate nonproliferative DR (NPDR) (n = 13), and advanced NPDR/proliferative DR (PDR) without vitreal hemorrhage (n = 14). None of the patients had been under anti-VEGF or laser treatment within six months prior to surgery. In the AH, TGF-β1 levels increased in advanced NPDR/PDR by a factor of 5.5 compared to the control group. Similarly, an increase in MMP-3 and TIMP-1 levels in the AH was evident in the later stages of DR, corresponding to a 7.7- and 2.4-fold increase compared to the control group, respectively, whereas serum levels of the studied proteins remained similar. In conclusion, increased concentrations of TGF-β1, MMP-3, and TIMP-1 in the AH, but not in the serum, in advanced NPDR/PDR indicate that the intraocular regulation for these cytokines is independent of the systemic one and suggest their involvement in the progression of DR

Risks and Challenges in Interpreting Simultaneous Analyses of Multiple Cytokines

Abstract Purpose: To determine the inherent risks of handling results below the lowest detectable value in the analysis of multiple cytokines in the aqueous humor of patients with retinal diseases by comparing possible statistical strategies to lower the risk of mis interpretation or over interpretation of results. Furthermore, in analyzing multiple cytokines simultaneously, the challenge of multiple comparison arises. Methods: The analyses were based on parallel testing of 43 cytokines in 58 aqueous humor samples from patients with macular hole or epiretinal membrane. Substitution of values below the detection limit with 0.1 ×, 0.5 ×, or 1.0× of the lowest level of quantitation was compared with handling as missing value. The impact of correction for multiple comparisons was assessed using the Holm correction. Results: When comparing macular hole with epiretinal membrane, not substituting the missing data revealed a difference (P < 0.05) for five compared with wight cytokines after their substitution, indicating an increased risk for under-estimating group differences (type II error). Correcting for multiple comparisons revealed a relevant risk of over estimating group differences (type I error). Conclusions: Physiologic cytokine concentrations in ocular fluids typically range at or below the lowest level of quantitation. Handling of results below this cutoff as missing leads to increased type II errors. Not correcting for multiple comparisons increases the risk of a type I error. Taken together, both harbor a systematic inherent risk of misinterpretation of the results

Exploring Supervisor-Related Job Resources as Mediators between Supervisor Conflict and Job Attitudes in Hospital Employees

Background: Conservation of resources theory assumes loss of resources as a cause of job strain. In hospital work, conflicts with supervisors are tested to predict lower resources, that is, supervisory social support, participation possibilities, and appreciation. All three resources are expected to predict, in turn, experienced stress (job strain) and lower job satisfaction, lower affective commitment, and a higher resigned attitude towards the job (job attitudes). Methods: The sample included 1,073 employees from 14 Swiss hospitals (n = 604 nurses, n = 81 physicians, n = 135 medical therapists, and n = 253 technical and administrative staff). Of the total sample, 83.1% were female and 38.9% worked full-time. The median tenure was between 7 years and 10 years. Constructs were assessed by online questionnaires. Structural equation modeling was used to test mediation. Results: Structural equation modeling confirmed the negative association of conflict with supervisors and job resources. Tests of indirect paths to resources as a link between conflicts with supervisors and job attitudes were significant. For nurses, social support, participation and appreciation showed a significant indirect path, while among medical technicians the indirect paths included social support and appreciation, and among physicians only appreciation showed a significant indirect path. In medical therapists no indirect path was significant. Job resources did not mediate the link between conflict with supervisors and stress in any occupational group. Conclusion: Conflicts with supervisors are likely to reduce job resources and in turn to lower job attitudes. Work design in hospitals should, therefore, address interpersonal working conditions and conflict management in leadership development

Sleep, Work Stress and Headache in Printing Business: An Actigraphy Study

Purpose: Technological change, economic pressure and the need for concentration increase work stress in the printing busi-ness. It is well known that stress in the workplace is associated with impaired cognitive functioning, such as headaches and concentration problems. Accordingly, daily recovery—especially restful and healthy sleep—is essential for human functioning. This study tested whether the quality of the previous night’s sleep predicts headaches and concentration problems independent of current-day time pressure, work interruptions and concentration requirements. Methods: Twenty-seven out of 28 printing plant employees contributed daily data over five consecutive workdays. Self-reported data on working conditions and cognitive functions and actigraphy-based indicators of sleep quality were subjected to multi-level analysis. Results: Multilevel regression analysis of 125 days confirmed that longer sleep-onset latency, more fragmented sleep and lower sleep efficiency were antecedents of headache intensity the following day. Headaches were also predicted by the current work interruptions. Concentration problems were predicted by the previous night’s sleep latency and the current day’s concentration requirements. Conclusion: Poor recovery in the sense of low sleep quality may impair cognitive function beyond the effects of the current-day’s work stress. Work redesign and person-oriented training should be used to promote sleep and cognitive function in printers