Determinants of late presentation of glaucoma in Hong Kong.

BACKGROUND: Glaucoma is the commonest cause of irreversible blindness worldwide. As it is typically asymptomatic until advanced, the risk of blindness from late presentation is higher than other eye diseases. This study aims to investigate the risk factors for late presentation of primary glaucoma patients. METHODS: We undertook a hospital-based case-control study of a random sample of glaucoma patients from a hospital in Hong Kong. Structured questionnaires and existing information from the electronic patient record were used, and the odds of presenting late were analysed by logistic regression. RESULTS: Of 210 recruited participants, 83 (39.5%) presented with advanced glaucoma unilaterally or bilaterally. The mean age of participants was 61.1 ± 11.9 years, with 110 males (52.4%). Univariate analysis revealed that male sex and primary angle-closure glaucoma (PACG) have 3.06 (CI95:1.71-5.48; P < 0.001) and 2.47 (CI95:1.11-5.49; P = 0.03) times higher odds of late presentation, respectively. Multivariate analysis revealed late presenters were 3.54 (CI95:1.35-9.35; P = 0.01) times more likely to have PACG than primary open-angle glaucoma (POAG). Patients with elevated baseline intraocular pressure (IOP) also had 1.06 times higher odds of presenting with advanced glaucoma (CI95:1.02-1.11; P = 0.002). Linear regression revealed that PACG patients present with 7.12 mmHg higher IOP than POAG patients (CI95:4.23-10.0; P < 0.001). CONCLUSION: In conclusion, a high proportion of glaucoma patients present late in Hong Kong, with gender and type of glaucoma being significant determinants. Our study shows that PACG presents with higher IOP and, along with male gender, are more likely to have advanced disease than POAG

ExPRESS Mini-Shunt as a Treatment Alternative for Medically Uncontrolled Steroid-Induced Glaucoma in a Pediatric Patient

This case report illustrates the use of ExPRESS mini-shunt in a pediatric glaucoma patient. We describe the management of steroid-induced glaucoma with ExPRESS mini-shunt in a 9-year-old boy with allergic keratoconjunctivitis. The intraocular pressure of both of his eyes was uncontrolled with medical and laser treatment. Both eyes were treated with ExPRESS mini-shunt and mitomycin-C. Transient overfiltration with postoperative hypotony occurred in both eyes and resolved after 2 weeks. One year postoperatively, intraocular pressure was maintained below 21 mm Hg without medication in 1 eye. Bleb needling with mitomycin-C was done to maintain filtration. The fellow eye received cataract extraction but developed bleb failure a few months afterwards. The intraocular pressure was controlled medically. To conclude, ExPRESS mini-shunt is a new surgical option in selected patients. Bleb failure developed after cataract extraction. Postoperative inflammation should be minimized. Patient selection, such as those with stable ocular condition, is important to increase surgical success

Proactive infection control measures to prevent nosocomial transmission of vancomycin-resistant enterococci in Hong Kong

Background/Purpose: The study describes a proactive infection control approach to prevent nosocomial transmission of vancomycin-resistant enterococci (VRE) and tests if this approach is effective for controlling multiple-drug resistant organisms in a nonendemic setting. Methods: In response to the increasing prevalence of VRE in Hong Kong since 2011, we adopted a multifaceted assertive approach in our health care network. This included active surveillance culture, extensive contact tracing, directly observed hand hygiene in conscious patients before they received meals and medications, stringent hand hygiene and environmental cleanliness, and an immediate feedback antimicrobial stewardship program. We report the occurrence of VRE outbreaks in our hospital after institution of these measures and compared with the concurrent occurrence in other public hospitals in Hong Kong. Results: Between July 1, 2011 and November 13, 2013, VRE was identified in 0.32% (50/15,851) of admission episodes by active surveillance culture. The risk of VRE carriage was three times higher in patients with a history of hospitalization outside our hospital networks in the past 3 months (0.56% vs. 0.17%; p=0.001) compared with those who were not. Extensive contact tracing involving 3277 patient episodes was performed in the investigation for the 25 VRE index patients upon whom implementation of contact precautions was delayed (more than 48 hours of hospitalization). One episode of VRE outbreak was identified in our hospital network, compared with the 77 VRE outbreaks reported in the other hospital networks (controls) without these proactive infection control measures. Conclusion: Our multifaceted assertive proactive infection control approach can minimize the nosocomial transmission and outbreak of VRE in a nonendemic area. © 2014

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics

Correction: The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms (vol 36, pg 1720, 2022)

10.1038/s41375-023-01962-5LEUKEMIA3791944-195

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

Background Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. Methods PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. Findings Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. Interpretation Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p