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To determine the efficacy of repeat selective laser trabeculoplasty (SLT) in medication-naive open-angle glaucoma (OAG) and ocular hypertensive (OHT) patients requiring repeat treatment for early to medium-term failure during the Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. Post hoc analysis of SLT treatment arm of a multicenter prospective randomized controlled trial. Treatment-naive OAG or OHT requiring repeat 360-degree SLT within 18 months. Retreatment was triggered by predefined IOP and disease-progression criteria (using objective individualized target IOPs). After SLT at baseline, patients were followed for a minimum of 18 months after second (repeat) SLT. A mixed-model analysis was performed with the eye as the unit of analysis, with crossed random effects to adjust for correlation between fellow eyes and repeated measures within eyes. Kaplan–Meier curves plot the duration of effect. Initial (early) IOP lowering at 2 months and duration of effect after initial and repeat SLT. A total of 115 eyes of 90 patients received repeat SLT during the first 18 months of the trial. Pretreatment IOP before initial SLT was significantly higher than before retreatment IOP of repeat SLT (mean difference, 3.4 mmHg; 95% confidence interval [CI], 2.6–4.3 mmHg; P < 0.001). Absolute IOP reduction at 2 months was greater after initial SLT compared with repeat SLT (mean difference, 1.0 mmHg; 95% CI, 0.2–1.8 mmHg; P = 0.02). Adjusted absolute IOP reduction at 2 months (adjusting for IOP before initial or repeat laser) was greater after repeat SLT (adjusted mean difference, −1.1 mmHg, 95% CI, −1.7 to −0.5 mmHg; P = 0.001). A total of 34 eyes were early failures (retreatment 2 months after initial SLT) versus 81 later failures (retreatment >2 months after initial SLT). No significant difference in early absolute IOP reduction at 2 months after repeat SLT was noted between early and later failures (mean difference, 0.3 mmHg; 95% CI, −1.1 to 1.8 mmHg; P = 0.655). Repeat SLT maintained drop-free IOP control in 67% of 115 eyes at 18 months, with no clinically relevant adverse events. These exploratory analyses demonstrate that repeat SLT can maintain IOP at or below target IOP in medication-naive OAG and OHT eyes requiring retreatment with at least an equivalent duration of effect to initial laser. [ABSTRACT FROM AUTHOR]

To report clinical efficacy, predictors of success, and safety of primary selective laser trabeculoplasty (SLT) used in treatment-naive patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Post hoc analysis of a multicenter, prospective, randomized, controlled trial. Treatment-naive patients with OAG or OHT. Patients randomized to SLT or topical medication and treated to predefined target intraocular pressures (IOPs) requiring ≥20% IOP reduction from baseline for all disease severity levels. Initial (early) absolute IOP-lowering at 2 months. Achievement of drop-free disease-control: meeting target IOP without disease progression or need for additional topical medication over 36 months after SLT. Predictors of early absolute IOP-lowering and drop-free disease-control after single initial SLT. Frequency of laser-related complications. A total of 611 eyes (195 OHT and 416 OAG) of 355 patients received SLT, and 622 eyes (185 OHT and 437 OAG) of 362 patients received topical medication at baseline. Early absolute IOP-lowering after SLT was no different between OHT and OAG eyes (adjusted mean difference = −0.05 mmHg; 95% confidence interval [CI], −0.6 to 0.5 mmHg; P = 0.85). No difference was noted in early absolute IOP-lowering between topical medication and primary SLT (adjusted mean difference = −0.1 mmHg; 95% CI, −0.6 to 0.4 mmHg; P = 0.67). Early absolute IOP-lowering with primary SLT was positively associated with baseline IOP (coefficient 0.58; 95% CI, 0.53–0.63; P < 0.001) and negatively with female gender (coefficient −0.63; 95% CI, −1.23 to −0.02; P = 0.04). At 36 months, 536 eyes (87.7% of 611 eyes) of 314 patients (88.5% of 355 patients) were available for analysis. Some 74.6% of eyes (400 eyes) treated with primary SLT achieved drop-free disease-control at 36 months; 58.2% (312 eyes) after single SLT. Total SLT power and 2-month IOP were predictors of drop-free disease-control at 36 months after single SLT. Six eyes of 6 patients experienced immediate post-laser IOP spike (>5 mmHg from pretreatment IOP) with 1 eye requiring treatment. Primary SLT achieved comparable early absolute IOP-lowering in OHT versus OAG eyes. Drop-free disease-control was achieved in approximately 75% eyes at 36 months after 1 or 2 SLTs, the majority of these after single SLT. These analyses are exploratory but support primary SLT to be effective and safe in treatment-naive OAG and OHT eyes. [ABSTRACT FROM AUTHOR]

Objectives To review how multiple primary outcomes are currently considered in the analysis of randomised controlled trials. We briefly describe the methods available to safeguard the inferences and to raise awareness of the potential problems caused by multiple outcomes. Methods/design We reviewed randomised controlled trials (RCTs) in neurology and psychiatry disease areas, as these frequently analyse multiple outcomes. We reviewed all published RCTs from July 2011 to June 2014 inclusive in the following high impact journals: The New England Journal of Medicine, The Lancet, The American Journal of Psychiatry, JAMA Psychiatry, The Lancet Neurology and Neurology. We examined the information presented in the abstract and the methods used for sample size calculation and statistical analysis. We recorded the number of primary outcomes, the methods used to account for multiple primary outcomes, the number of outcomes discussed in the abstract and the number of outcomes used in the sample size calculation. Results Of the 209 RCTs that we identified, 60 (29%) analysed multiple primary outcomes. Of these, 45 (75%) did not adjust for multiplicity in their analyses. Had multiplicity been addressed, some of the trial conclusions would have changed. Of the 15 (25%) trials which accounted for multiplicity, Bonferroni's correction was the most commonly used method. Conclusions Our review shows that trials with multiple primary outcomes are common. However, appropriate steps are not usually taken in most of the analyses to safeguard the inferences against multiplicity. Authors should state their chosen primary outcomes clearly and justify their methods of analysis. [ABSTRACT FROM AUTHOR]

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial has shown selective laser trabeculoplasty (SLT) to be clinically and cost-effective as a primary treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT) at 3 years. This article reports health-related quality of life (HRQoL) and clinical effectiveness of initial treatment with SLT compared with intraocular pressure (IOP)-lowering eye drops after 6 years of treatment. Prospective, multicenter randomized controlled trial. Treatment-naive eyes with OAG or OHT initially treated with SLT or IOP-lowering drops. Patients were allocated randomly to initial SLT or eye drops. After the initial 3 years of the trial, patients in the SLT arm were permitted a third SLT if necessary; patients in the drops arm were allowed SLT as a treatment switch or escalation. This study is registered at controlled-trials.com (identifier, ISRCTN32038223). The primary outcome was HRQoL at 6 years; secondary outcomes were clinical effectiveness and adverse events. Of the 692 patients completing 3 years in the LiGHT Trial, 633 patients (91.5%) entered the extension, and 524 patients completed 6 years in the trial (82.8% of those entering the extension phase). At 6 years, no significant differences were found for the EuroQol EQ-5D 5 Levels, Glaucoma Utility Index, and Glaucoma Quality of Life-15 (P > 0.05 for all). The SLT arm showed better Glaucoma Symptom Scale scores than the drops arm (83.6 ± 18.1 vs. 81.3 ± 17.3, respectively). Of eyes in the SLT arm, 69.8% remained at or less than the target IOP without the need for medical or surgical treatment. More eyes in the drops arm exhibited disease progression (26.8% vs. 19.6%, respectively; P = 0.006). Trabeculectomy was required in 32 eyes in the drops arm compared with 13 eyes in the SLT arm (P < 0.001); more cataract surgeries occurred in the drops arm (95 compared with 57 eyes; P = 0.03). No serious laser-related adverse events occurred. Selective laser trabeculoplasty is a safe treatment for OAG and OHT, providing better long-term disease control than initial drop therapy, with reduced need for incisional glaucoma and cataract surgery over 6 years. [ABSTRACT FROM AUTHOR]

In patients with advanced cancer, prognosis is usually determined using clinicians' predictions of survival (CPS). The palliative prognostic (PaP) score is a prognostic algorithm that was developed to predict survival in patients with advanced cancer. The score categorises patients into three risk groups in accordance with their probability of surviving for 30 days. The relative accuracy of PaP and CPS is unclear. This was a systematic review of MEDLINE, Embase, AMED, CINAHL Plus and the Cochrane Database of Systematic Reviews and Trials from inception up to June 2021. The inclusion criteria were studies in adults with advanced cancer reporting data on performance of both PaP and CPS. Data were extracted on accuracy of prognoses and where available on discrimination (area under the receiver operating characteristic curve or C-index) and/or diagnostic performance (sensitivity, specificity). Eleven studies were included. One study reported a direct comparison between PaP risk groups and equivalent risk groups defined by CPS and found that PaP was as accurate as CPS. Five studies reported discrimination of PaP as a continuous total score (rather than using the previously validated risk categories) and reported C-statistics that ranged from 0.64 (95% confidence interval [CI] 0.54, 0.74) up to 0.90 (95% CI 0.87, 0.92). Other studies compared PaP against CPS using non-equivalent metrics (e.g. comparing probability estimates against length of survival estimates). PaP risk categories and CPS are equally able to discriminate between patients with different survival probabilities. Total PaP scores show good discrimination between patients in accordance with their length of survival. The role of PaP in clinical practice still needs to be defined. PROSPERO (CRD42021241074, 5th March 2021). • The palliative prognostic (PaP) score predicts the risk of dying within 30 days. • PaP is as accurate as, but not better than, clinical predictions of 30-day survival. • The relative objectivity of PaP may help supplement clinical predictions. [ABSTRACT FROM AUTHOR]