Topographical Response of Retinal Neovascularization to Aflibercept or Panretinal Photocoagulation in Proliferative Diabetic Retinopathy Post Hoc Analysis of the CLARITY Randomized Clinical Trial

Importance Eyes with proliferative diabetic retinopathy have a variable response to treatment with panretinal photocoagulation (PRP) or anti–vascular endothelial growth factor agents. The location of neovascularization (NV) is associated with outcomes (eg, patients with disc NV [NVD] have poorer visual prognosis than those with NV elsewhere [NVE]). Objective To investigate the distribution of NV in patients with proliferative diabetic retinopathy and the topographical response of NV to treatment with aflibercept or PRP. Design, Setting, and Participants This post hoc analysis of the phase 2b randomized clinical single-masked multicenter noninferiority Clinical Efficacy and Mechanistic Evaluation of Aflibercept for Proliferative Diabetic Retinopathy (CLARITY) trial was conducted from November 1, 2019, to September 1, 2020, among 120 treatment-naive patients with proliferative diabetic retinopathy to evaluate the topography of NVD and NVE in 4 quadrants of the retina on color fundus photography at baseline and at 12 and 52 weeks after treatment. Exposures In the CLARITY trial, patients were randomized to receive intravitreal aflibercept (2 mg/0.05 mL at baseline, 4 weeks, and 8 weeks, and as needed from 12 weeks onward) or PRP (completed in initial fractionated sessions and then on an as-needed basis when reviewed every 8 weeks). Main Outcomes and Measures Main outcomes were per-retinal quadrant frequencies of NV at baseline and frequencies of patterns of regression, recurrence, and new occurrence at 12-week and 52-week unmasked follow-up. Results The study included 120 treatment-naive patients (75 men; mean [SD] age, 54.8 [14.6] years) with proliferative diabetic retinopathy (there was a 1:1 ratio of eyes to patients). At baseline, NVD with or without NVE was observed in 42 eyes (35.0%), and NVE only was found in 78 eyes (65.0%); NVE had a predilection for the nasal quadrant (64 [53.3%]). Rates of regression with treatment were higher among eyes with NVE (89 of 102 [87.3%]) compared with eyes with NVD (23 of 43 [53.5%]) by 52 weeks, with NVD being more resistant to either treatment with higher rates of persistence than NVE (20 of 39 [51.3%] vs 29 of 100 [29.0%]). Considering NVE, the regression rate in the temporal quadrant was lowest (32 of 42 [76.2%]). Eyes treated with aflibercept showed higher rates of regression of NVE compared with those treated with PRP (50 of 52 [96.2%] vs 39 of 50 [78.0%]; difference, 18.2% [95% CI, 5.5%-30.8%]; P = .01), but no difference was found for NVD (11 of 17 [64.7%] vs 12 of 26 [46.2%]; difference, 18.6% [95% CI, −11.2% to 48.3%]; P = .23). Conclusions and Relevance This post hoc analysis found that NVD is less frequent but is associated with more resistance to currently available treatments than NVE. Aflibercept was superior to PRP for treating NVE, but neither treatment was particularly effective against NVD by 52 weeks. Future treatments are needed to better target NVD, which has poorer visual prognosis. Trial Registration isrctn.org Identifier: ISRCTN3220758

Can early warning scores identify deteriorating patients in pre-hospital settings? A systematic review

OBJECTIVE: To evaluate the effectiveness and predictive accuracy of early warning scores (EWS) to predict deteriorating patients in pre-hospital settings. METHODS: Systematic review. Seven databases searched to August 2017. Study quality was assessed using QUADAS-2. A narrative synthesis is presented. ELIGIBILITY: Studies that evaluated EWS predictive accuracy or that compared outcomes in populations that did or did not use EWS, in any pre-hospital setting were eligible for inclusion. EWS were included if they aggregated three or more physiological parameters. RESULTS: Seventeen studies (157,878 participants) of predictive accuracy were included (16 in ambulance service and 1 in nursing home). AUCs ranged from 0.50 (CI not reported) to 0.89 (95%CI 0.82, 0.96). AUCs were generally higher (>0.80) for prediction of mortality within short time frames or for combination outcomes that included mortality and ICU admission. Few patients with low scores died at any time point. Patients with high scores were at risk of deterioration. Results were less clear for intermediate thresholds (≥4 or 5). Five studies were judged at low or unclear risk of bias, all others were judged at high risk of bias. CONCLUSIONS: Very low and high EWS are able to discriminate between patients who are not likely and those who are likely to deteriorate in the pre-hospital setting. No study compared outcomes pre- and post-implementation of EWS so there is no evidence on whether patient outcomes differ between pre-hospital settings that do and do not use EWS. Further studies are required to address this question and to evaluate EWS in pre-hospital settings

Systematic review of interventions for the prevention and treatment of postoperative urinary retention

Background: Postoperative urinary retention (PO‐UR) is an acute and painful inability to void after surgery that can lead to complications and delayed hospital discharge. Standard treatment with a urinary catheter is associated with a risk of infection and can be distressing, undignified and uncomfortable. This systematic review aimed to identify effective interventions for the prevention and treatment of PO‐UR that might be alternatives to urinary catheterization. Methods: Electronic databases were searched from inception to September 2017. Randomized trials of interventions for the prevention or treatment of PO‐UR were eligible for inclusion. Studies were assessed for risk of bias using the Cochrane (2.0) tool. Two reviewers were involved at all review stages. Where possible, data were pooled using random‐effects meta‐analysis. The overall quality of the body of evidence was rated using the GRADE approach. Results: Some 48 studies involving 5644 participants were included. Most interventions were pharmacological strategies to prevent PO‐UR. Based on GRADE, there was high‐certainty evidence to support replacing morphine in a regional anaesthetic regimen, using alpha‐blockers (number needed to treat to prevent one case of PO‐UR (NNT) 5, 95 per cent c.i. 5 to 7), the antispasmodic drug drotaverine (NNT 9, 7 to 30) and early postoperative mobilization (NNT 5, 4 to 8) for prevention, and employing hot packs or gauze soaked in warm water for treatment (NNT 2, 2 to 4). Very few studies reported on secondary outcomes of pain, incidence of urinary tract infection or duration of hospital stay. Conclusion: Promising interventions exist for PO‐UR, but they need to be evaluated in randomized trials investigating comparative clinical and cost effectiveness, and acceptability to patients