Facedown Positioning in Macular Hole Surgery: A Systematic Review and Individual Participant Data Meta-Analysis.

TOPIC: To assess the anatomic and visual effects of facedown positioning (FDP) advice in patients undergoing vitrectomy with gas tamponade for idiopathic full-thickness macular holes (FTMHs) and to explore differential treatment effects by macular hole size and FDP duration. CLINICAL RELEVANCE: The necessity and duration of FDP for FTMH closure remain contentious, with no consensus guidelines. METHODS: Prospectively registered systematic review and individual patient data (IPD) meta-analysis of randomized controlled trials comparing FDP with no FDP (nFDP) across the MEDLINE, Embase, and Cochrane Library databases and clinical trial registries from January 2000 to March 2023 (CRD42023395152). All adults with idiopathic FTMHs undergoing vitrectomy with gas tamponade were included. The main outcomes were primary macular hole closure and postoperative visual acuity at 6 months or nearest time point. RESULTS: Of 8 eligible trials, 5 contributed IPD for 379 eyes and were included in our analysis. The adjusted odds ratio (OR) for primary closure with FDP versus nFDP was 2.41 (95% confidence interval [CI], 0.98-5.93, P = 0.06; low-certainty evidence), translating to a risk ratio (RR) of 1.08 (1.00-1.11) and a number needed to treat (NNT) of 15. The FDP group exhibited a mean improvement in postoperative visual acuity of -0.08 logarithm of the minimum angle of resolution (logMAR) (-0.13 to -0.02, P = 0.006; low-certainty evidence) compared with the nFDP group. Benefits were more certain in participants with larger holes of minimum linear diameter ≥ 400 µm: adjusted OR for closure ranged from 1.13 to 10.12 (P = 0.030) (NNT 12), with a mean visual acuity improvement of -0.18 to -0.01 logMAR (P = 0.022). Each additional day of FDP was associated with improved odds of anatomic success (adjusted OR, 1.02-1.41, RR, 1.00-1.02, P = 0.026) and visual acuity improvement (-0.02 logMAR, -0.03 to -0.01, P = 0.002), possibly plateauing at 3 days. CONCLUSIONS: This study provides low-certainty evidence that FDP improves the anatomic and visual outcomes of macular hole surgery modestly and indicates that the effect may be more substantial for macular holes exceeding 400 µm. The findings support recommending FDP for patients with macular holes exceeding 400 µm pending further investigation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Cost-effectiveness analysis of the Geriatric Fracture Center (GFC) concept: a prospective multicentre cohort study.

INTRODUCTION: Geriatric Fracture Centers (GFCs) are dedicated treatment units where care is tailored towards elderly patients who have suffered fragility fractures. The primary objective of this economic analysis was to determine the cost-utility of GFCs compared with usual care centres. METHODS: The primary analysis was a cost-utility analysis that measured the cost per incremental quality-adjusted life-year gained from treatment of hip fracture in GFCs compared with treatment in usual care centres from the societal perspective over a 1-year time horizon. The secondary analysis was a cost-utility analysis from a societal perspective over a lifetime time horizon. We evaluated these outcomes using a cost-utility analysis using data from a large multicentre prospective cohort study comparing GFCs versus usual care centres that took place in Austria, Spain, the USA, the Netherlands, Thailand and Singapore. RESULTS: GFCs may be cost-effective in the long term, while providing a more comprehensive care plan. Patients in usual care centre group were slightly older and had fewer comorbidities. For the 1-year analysis, the costs per patient were slightly lower in the GFC group (-$646.42), while the quality-adjusted life-years were higher in the usual care centre group (+0.034). The incremental cost-effectiveness ratio was $18 863.34 (US$/quality-adjusted life-year). The lifetime horizon analysis found that the costs per patient were lower in the GFC group (-$7210.35), while the quality-adjusted life-years were higher in the usual care centre group (+0.02). The incremental cost-effectiveness ratio was $320 678.77 (US$/quality-adjusted life-year). CONCLUSIONS: This analysis found that GFCs were associated with lower costs compared with usual care centres. The cost-savings were greater when the lifetime time horizon was considered. This comprehensive cost-effectiveness analysis, using data from an international prospective cohort study, found that GFC may be cost-effective in the long term, while providing a more comprehensive care plan. A greater number of major adverse events were reported at GFC, nevertheless a lower mortality rate associated with these adverse events at GFC. Due to the minor utility benefits, which may be a result of greater adverse event detection within the GFC group and much greater costs of usual care centres, the GFC may be cost-effective due to the large cost-savings it demonstrated over the lifetime time horizon, while potentially identifying and treating adverse events more effectively. These findings suggest that the GFC may be a cost-effective option over the lifetime of a geriatric patient with hip fracture, although future research is needed to further validate these findings. LEVEL OF EVIDENCE: Economic, level 2. TRIAL REGISTRATION NUMBER: NCT02297581.

Role of Positioning after Full-Thickness Macular Hole Surgery: A Systematic Review and Meta-Analysis.

TOPIC: The importance of postoperative face-down positioning (FDP) to achieve anatomic and functional success after full-thickness macular hole (FTMH) surgery is explored in this meta-analysis of randomized controlled trials (RCTs). CLINICAL RELEVANCE: There is considerable variability in clinical practices regarding the need and length of FDP recommended to patients after FTMH surgery. There is also a lack of robust clinical guidelines on the topic. As such, an updated estimate of the effect size of FDP on clinically important outcomes is critical to inform practice. METHODS: Ovid MEDLINE, EMBASE, CENTRAL, and SCOPUS databases were searched from inception to October 3, 2021, for RCTs evaluating FDP versus non-FDP (nFDP). Data were collected for 7 clinically important outcomes after macular hole surgery: closure rate, visual acuity (VA) improvement, recurrence of FTMH, visual function, quality of life, patient satisfaction, and complication rates. We used the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the risk of bias and followed the Grade of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty in the evidence across outcomes. We conducted meta-analyses using random-effects modeling. Subgroup analyses were carried out based on hole size, type of gas, and duration of FDP. RESULTS: Eight RCTs of 709 eyes were included. The relative risk (RR) of FTMH closure rate comparing FDP versus nFDP was RR 1.05 (95% confidence interval [CI]: 0.99, 1.12, P = 0.09, I2 = 44%, GRADE rating: LOW). The mean difference (MD) regarding VA improvement comparing FDP and nFDP was MD -0.07 (95% CI: -0.12 to 0.01, P = 0.03, I2 = 16%, GRADE rating: LOW). CONCLUSION: The current review did not demonstrate a difference between FDP and nFDP with respect to FTMH closure, although the CIs were wide. There was a visual benefit to FDP; however, the CIs included values of trivial clinical significance. Subgroup analyses demonstrated that the VA benefit observed was driven by large holes. Limited data precluded analysis regarding the rate of FTMH recurrence, measures of visual function, quality of life measures, and patient satisfaction metrics. Further prospective trials are required to assess the gaps in the literature and improve the certainty of evidence for the outcomes examined.

Role of anti-vascular endothelial growth factor in the management of non-proliferative diabetic retinopathy without centre-involving diabetic macular oedema: a meta-analysis of trials.

This systematic review and meta-analysis investigated the impact of anti-vascular endothelial growth factor (VEGF) treatment in management of eyes with non-proliferative diabetic retinopathy (NPDR) without centre involving diabetic macular oedema (CI-DMO). We searched multiple databases for all randomised clinical trials (RCTs) that evaluated anti-VEGF treatment versus observation in eyes with NPDR without CI-DMO. Data was collected for six outcomes (best corrected visual acuity (BCVA) improvement, diabetic retinopathy severity score (DRSS), central subfield thickness, progression to vision threatening complications (VTCs), ocular adverse events and quality of life measures). Risk of bias was assessed using Cochrane risk-of-bias tool for randomised trials (RoB 2) and certainty of evidence was assessed using Grade of Recommendations, Assessment, Development and Evaluation (GRADE). We identified a total of 2 unique RCTs that compared aflibercept and sham to treat a total of 811 eyes. For BCVA change, there was a small, clinically insignificant benefit for aflibercept treatment at year 2 (MD 0.70, 95% CI 0.02-1.38, GRADE rating: MODERATE). DRSS demonstrated a statistically significant improvement with aflibercept use at year 2 (RR 3.76, 95% CI 2.75-5.13, GRADE rating: MODERATE). VTCs were significantly less in aflibercept arm at year 2 (RR 0.30, 95% CI 0.23-0.40, GRADE rating: MODERATE). In conclusion, aflibercept treatment versus observation in eyes with NPDR without CI-DMO can result in reduced risk of development of VTCs and regression of DRSS score over 2 years. Future trials are needed to increase the precision of the treatment effect and to provide data on quality-of-life metrics.PROSPERO Registration: CRD42021288608.

Efficacy, safety, and treatment burden of treat-and-extend versus alternative anti-VEGF regimens for nAMD: a systematic review and meta-analysis.

This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related macular degeneration (nAMD). MEDLINE, CENTRAL, and EMBASE were searched. Randomized-controlled trials and observational studies comparing T&E to PRN or fixed dosing for treatment-naïve AMD patients were included. Mean difference (MD) for visual acuity (VA) and number of injections are presented. Risk of bias was assessed according to Cochrane guidelines. Methodology was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). VA improvement was similar with T&E and fixed dosing at one (MD -0.08 letters, p = 0.95) and two years (MD 0.58 letters, p = 0.62). In contrast, VA improvements were significantly greater for T&E when compared against a PRN regimen at one (MD 3.95 letters, p < 0.0001) and two years (MD 4.08 letters, p < 0.001). Significantly fewer ranibizumab injections were administered in the T&E arm at one (MD -2.42 injections, p < 0.0001) and two years (MD -6.06 injections, p < 0.00001) relative to fixed dosing. Fewer aflibercept injections were likewise administered to patients on a T&E regimen versus fixed dosing at one year (MD -0.78 injections, p < 0.0001). Low-certainty evidence from the present synthesis implies that T&E preserves VA similar to fixed schedules with significantly fewer injections at one and two years. Also, patients with T&E dosing achieved better VA outcomes than those on PRN regimen but T&E dosing was associated with more injections.

Surveying Canadian Pain Physicians' Attitudes and Beliefs Regarding Medical Cannabis for Chronic Noncancer Pain: A Qualitative Study.

Background: Medical cannabis is commonly and increasingly used by Canadians to manage chronic pain. As of March 2021, Health Canada reported that approximately 300,000 Canadians who were authorized to access medical cannabis, which is more than a 1000% increase from the 24,000 registered in 2015. Physicians, however, receive limited information on therapeutic cannabis during their training, and their perceptions regarding this therapeutic option are uncertain. This study focused on exploring attitudes and beliefs of pain physicians regarding medical cannabis for the management of chronic noncancer pain. Methods: This study utilized a focused ethnography approach. Pain management clinicians within the Greater Toronto and Hamilton Area were recruited through snowball sampling methods, and individually interviewed. We applied thematic analysis to interview transcripts and identified representative quotes. The Hamilton Integrated Research Ethics Board reviewed and approved this project. Results: Thirteen physicians who focused their clinical practice on pain management agreed to be interviewed, and three themes regarding medical cannabis emerged: 1) evidence regarding medical cannabis, 2) medical cannabis as first-line therapy for chronic pain, and 3) barriers to accessing medical cannabis. Subthemes of the last theme included out-of-pocket costs, stigma by society and healthcare providers, and lack of knowledge among physicians. Conclusion: Despite increasing use of medical cannabis for chronic pain among Canadians, pain physicians in our study expressed concerns regarding the evidence to support this therapy and acknowledged important barriers to access.

A scoping review of operative and non-invasive management in the treatment of non-unions.

INTRODUCTION: Non-union occurs when a fracture fails to adequately heal, and requires additional intervention to achieve union. The purpose of this scoping review is to provide a high-level overview of the existing non-union management literature. This review aims to highlight the current literature on non-union management, as well as identify key areas that require future research to provide a better understanding of potential non-union management strategies. METHODS: This study utilized the scoping review framework from Arksey and O'Malley All relevant literature on non-union management was systematically searched for within the OVID Medline, OVID Embase, and Web of Science databases. As a scoping review, this study aimed to identify the high-level trends in non-union literature. This was assessed through a visual and numerical summary of the general themes in non-union literature, as well as the timeline in which these trends have occurred. RESULTS: The literature search identified 8081 articles, of which 2210 articles were included. There is a large body of evidence for various surgical treatment options for non-union. The literature suggests healing rates between 80 and 100 percent for commonly utilized surgical procedures, such as plating with bone graft for long bones. Despite these beneficial healing rates, the requirement of a surgery creates a large socioeconomic burden. The possibility for bone growth stimulator (BGS) options to achieve non-union healing rates in a similar realm as surgical options suggests that the use of a BGS may be a beneficial option prior to surgical intervention, as this would potentially reduce the number of patients who would otherwise require surgery. CONCLUSION: A large body of evidence exists on non-union management, which is largely comprised of case series and reports. The most commonly assessed non-unions include the tibia, wrist, and femur. Bone grafting, plating, and nailing are the most investigated treatment options. BGS are a non-operative treatment options for non-union that provide similar healing rates to surgical options in certain indications within initial observational data. BGS are a potential option for non-operative management of non-unions to reduce socioeconomic burdens of surgical intervention, with a need for further high-quality investigation in this therapeutic area.

Development and design validation of a novel network meta-analysis presentation tool for multiple outcomes: a qualitative descriptive study.

OBJECTIVE: The Grades of Recommendations, Assessment, Development and Evaluation working group recently developed an innovative approach to interpreting results from network meta-analyses (NMA) through minimally and partially contextualised methods; however, the optimal method for presenting results for multiple outcomes using this approach remains uncertain. We; therefore, developed and iteratively modified a presentation method that effectively summarises NMA results of multiple outcomes for clinicians using this new interpretation approach. DESIGN: Qualitative descriptive study. SETTING: A steering group of seven individuals with experience in NMA and design validation studies developed two colour-coded presentation formats for evaluation. Through an iterative process, we assessed the validity of both formats to maximise their clarity and ease of interpretation. PARTICIPANTS: 26 participants including 20 clinicians who routinely provide patient care, 3 research staff/research methodologists and 3 residents. MAIN OUTCOME MEASURES: Two team members used qualitative content analysis to independently analyse transcripts of all interviews. The steering group reviewed the analyses and responded with serial modifications of the presentation format. RESULTS: To ensure that readers could easily discern the benefits and safety of each included treatment across all assessed outcomes, participants primarily focused on simple information presentations, with intuitive organisational decisions and colour coding. Feedback ultimately resulted in two presentation versions, each preferred by a substantial group of participants, and development of a legend to facilitate interpretation. CONCLUSION: Iterative design validation facilitated the development of two novel formats for presenting minimally or partially contextualised NMA results for multiple outcomes. These presentation approaches appeal to audiences that include clinicians with limited familiarity with NMAs.

Treat-and-extend versus alternate dosing strategies with anti-vascular endothelial growth factor agents to treat center involving diabetic macular edema: A systematic review and meta-analysis of 2,346 eyes.

Anti-vascular endothelial growth factor (Anti-VEGF) agents are the standard of care for diabetic macular edema (CI-DME) with vision loss. They are commonly administered using several treatment protocols, including fixed, pro re nata (PRN) and treat-and-extend (T&E) regimens. Because of the lack of evidence defining an ideal treatment paradigm, we systematically compared T&E with fixed or PRN regimens. Visual acuity improvement was similar when comparing T&E to fixed or PRN dosing at 12 and 24 months. Regarding anatomic outcomes, no significant difference was found between T&E and fixed regimens for central retinal thickness or central subfoveal thickness at 12 and 24 months. Similarly, no significant difference was found for central retinal thickness at 12 months for T&E versus PRN regimen. Regarding total number of injections, no significant difference existed between T&E versus fixed regimens at 12 months. PRN regimens delivered fewer injections compared to T&E regimens at 12 months. The results of this analysis support that visual acuity and anatomic outcomes at 12 and 24 months are similar between T&E with either fixed or PRN regimens. More head-to-head trials comparing T&E versus fixed and PRN dosing are needed to provide visual and functional outcome data beyond year 2. PROSPERO Registration: CRD42021249362.