Anti-vascular endothelial growth factor therapy for age-related macular degeneration: a systematic review and network meta-analysis.

BACKGROUND: The comparative safety and efficacy between anti-vascular endothelial growth factor agents (anti-VEGFs) and between combined therapies for patients with neovascular age-related macular degeneration (nAMD) is unclear. We conducted a systematic review to examine the comparative safety and efficacy anti-VEGFs for adults with nAMD. METHODS: Studies were identified through MEDLINE, EMBASE, and Cochrane CENTRAL (inception to June 3, 2019), grey literature, and scanning reference lists. Two reviewers independently screened citations and full-text articles to identify randomized controlled trials (RCTs), extracted data, and appraised risk of bias. Pairwise random-effects meta-analysis and Bayesian network meta-analysis (NMA) were conducted. The primary outcomes were the proportion of patients experiencing moderate vision gain (≥ 15 letters on the Early Treatment Diabetic Retinopathy Study chart) and the proportion of patients experiencing moderate vision loss (≤ 15 letters). RESULTS: After screening 3647 citations and 485 potentially relevant full-text articles, 92 RCTs with 24,717 patients were included. NMA (34 RCTs, 8809 patients, 12 treatments) showed small differences among anti-VEGFs in improving the proportion of patients with moderate vision gain, with the largest for conbercept versus broluczumab (OR 0.15, 95% CrI: 0.05-0.56), conbercept versus ranibizumab (OR 0.17, 95% CrI: 0.05-0.59), conbercept versus aflibercept (OR 0.19, 95% CrI: 0.06-0.65), and conbercept versus bevacizumab (OR 0.2, 95% CrI: 0.06-0.69). In NMA (36 RCTs, 9081 patients, 13 treatments) for the proportion of patients with moderate vision loss, small differences were observed among anti-VEGFs, with the largest being for conbercept versus aflibercept (OR 0.24, 95% CrI: 0-4.29), conbercept versus brolucizumab (OR 0.24, 95% CrI: 0-4.71), conbercept versus bevacizumab (OR 0.26, 95% CrI: 0-4.65), and conbercept versus ranibizumab (OR 0.27, 95% CrI: 0-4.67). CONCLUSION: The only observed differences were that ranibizumab, bevacizumab, aflibercept, and brolucizumab were statistically superior to conbercept in terms of the proportion of patients with nAMD who experienced moderate vision gain. However, this finding is based on indirect evidence through one small trial comparing conbercept with placebo. This does not account for drug-specific differences when assessing anatomic and functional treatment efficacy in variable dosing regimens. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42015022041.

Exploring the prevalence of gaming disorder and Internet gaming disorder: a rapid scoping review.

BACKGROUND: Internet gaming disorder (IGD) was included in the DSM-5 in 2013 as a condition requiring further research, and gaming disorder (GD) was included in the ICD-11 in 2018. Given the importance of including these conditions in diagnostic guidelines, a review was conducted to describe their prevalence. METHODS: Using guidance from the Joanna Briggs Institute and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), we conducted a rapid scoping review. MEDLINE, Embase, PsycINFO, and the Cochrane library were searched for literature published from inception to July 2018. All review stages were pilot-tested to calibrate reviewers. The titles/abstracts and full-text articles were screened by one reviewer to include quantitative primary studies that reported GD or IGD prevalence. Excluded citations were screened by a second reviewer to confirm exclusion. Charting was conducted by one reviewer and verified by another, to capture relevant data. Results were summarized descriptively in tables or text. RESULTS: We assessed 5550 potentially relevant citations. No studies on GD were identified. We found 160 studies of various designs that used 35 different methods to diagnose IGD. The prevalence of IGD ranged from 0.21-57.50% in general populations, 3.20-91.00% in clinical populations, and 50.42-79.25% in populations undergoing intervention (severe cases). Most studies were conducted in the Republic of Korea (n = 45), China (n = 29), and the USA (n = 20). Results are also presented for severe IGD and by geographic region, gender/sex, and age groups (child, adolescent, adult). The five most frequently reported health-related variables were depression (67 times), Internet addiction (54 times), anxiety (48 times), impulsiveness (37 times), and attention-deficit hyperactivity disorder (24 times). CONCLUSIONS: Due to the variability in diagnostic approaches, knowledge users should interpret the wide IGD prevalence ranges with caution. In addition to further research on GD, consensus on the definition of IGD and how it is measured is needed, to better understand the prevalence of these conditions.

Interventions for the prevention and management of occupational stress injury in first responders: a rapid overview of reviews.

BACKGROUND: First responders are a high-risk population for occupational stress injuries as they often encounter prolonged stress within their line of work. The aim of this rapid overview of reviews is to summarize existing evidence on interventions for the prevention and management of occupational stress injury (OSI) in first responders. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science, and Cochrane Library were searched for systematic reviews examining the impact of prevention, rehabilitation, and resilience-building strategies targeting frontline community safety personnel in February 2019. Pairs of reviewers screened titles and abstracts followed by full-text articles and conducted data abstraction and quality appraisal using the AMSTAR II tool. To ensure a rapid overview process, the search strategy was limited to the last 10 years, quality appraisal of reviews and abstraction of study-level data was completed by one person and verified by another, and the quality of the individual primary studies was not appraised. The findings were summarized descriptively. RESULTS: A total of 14 reviews with 47 unique primary studies were found after screening 1393 records. A majority of studies targeted OSI in police officers (78.7%), followed by firefighters (17%) and correctional officers (4.3%). Of the 47 included primary studies, 24 targeted prevention of OSI (i.e., resilience training, stress management, suicide prevention, and other health promotions) and 23 targeted rehabilitation (i.e., drug therapy, psychotherapy, and other therapies). Prevention strategies including resilience training programs had positive outcomes, while suicide prevention and psychotherapy interventions reported mixed results. CONCLUSIONS: Some promising interventions targeting the prevention and rehabilitation of OSI among police officers, firefighters, and correctional officers were identified in the included studies, and these results will serve as a basis for the development of evidence-based strategies to mitigate future risks in this population. However, several gaps were also identified in this area that will require further investigation prior to widespread implementation of effective interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019125945.

Anti-vascular endothelial growth factor treatment for retinal conditions: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV). DESIGN: Systematic review and random-effects meta-analysis. METHODS: Multiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged ≥18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias. RESULTS: 19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6-9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients. CONCLUSIONS: Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (≥15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen. PROSPERO REGISTRATION NUMBER: CRD42015022041.

Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis.

OBJECTIVE: To compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older. DESIGN: Systematic review with bayesian meta-analysis and network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Experimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death. RESULTS: 27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively). CONCLUSIONS: Using the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites. PROTOCOL REGISTRATION: Prospero CRD42017056389.