Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease

OBJECTIVES: To investigate the course of interstitial lung disease (ILD) and the effects of nintedanib in patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: In the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib or placebo. Patients who completed the SENSCIS trial were eligible to enter SENSCIS-ON, in which all patients received open-label nintedanib. RESULTS: Among 277 patients with lcSSc treated in the SENSCIS trial, the rate (SE) of decline in FVC (mL/year) over 52 weeks was -74.5 (19.2) in the placebo group and -49.1 (19.8) in the nintedanib group (difference: 25.3 [95% CI -28.9, 79.6]). Among 249 patients with data at week 52, mean (SE) changes in FVC at week 52 were -86.4 (21.1) mL in the placebo group and -39.1 (22.2) mL in the nintedanib group. Among 183 patients with lcSSc who participated in SENSCIS-ON and had data at week 52, mean (SE) changes in FVC from baseline to week 52 of SENSCIS-ON were -41.5 (24.0) mL in patients who took placebo in the SENSCIS trial and initiated nintedanib in SENSCIS-ON and -45.1 (19.1) mL in patients who took nintedanib in the SENSCIS trial and continued it in SENSCIS-ON. CONCLUSION: Patients with lcSSc may develop progressive fibrosing ILD. By targeting pulmonary fibrosis, nintedanib slows decline in lung function in patients with lcSSc and ILD. TRIAL REGISTRATION: ClinicalTrials.gov (https://www.clinicaltrials.gov), NCT02597933 and NCT03313180

Gel stent versus trabeculectomy: The randomized, multicenter, Gold-Standard Pathway Study (GPS) of effectiveness and safety at 12 months

PURPOSE: To compare effectiveness and safety of the gel stent to trabeculectomy in open-angle glaucoma (OAG). DESIGN: Prospective, randomized, multicenter, noninferiority study. METHODS: Patients with OAG and intraocular pressure (IOP) 15 to 44 mm Hg on topical IOP-lowering medication were randomized 2:1 to gel stent implantation or trabeculectomy. Primary end point (surgical success): percentage of patients at month 12 achieving ≥20% IOP reduction from baseline without medication increase, clinical hypotony, vision loss to counting fingers, or secondary surgical intervention (SSI) in a noninferiority test with 24% margins. Secondary end points (month 12) included mean IOP and medication count, postoperative intervention rate, visual recovery, and patient-reported outcomes (PROs). Safety end points included adverse events (AEs). RESULTS: At month 12, the gel stent was statistically noninferior to trabeculectomy (between-treatment difference [Δ], -6.1%; 95% CI, -22.9%, 10.8%); 62.1% and 68.2% achieved the primary end point, respectively (P=.487); mean IOP and medication count reductions from baseline were significant (P\u3c.001); and the IOP change-related Δ (2.8 mm Hg) favored trabeculectomy (P=.024). The gel stent resulted in fewer eyes requiring in-office postoperative interventions (P=.024 after excluding laser suture lysis), faster visual recovery (P≤.048), and greater 6-month improvements in visual function problems (ie, PROs; P≤.022). The most common AEs were reduced visual acuity at any time (gel stent, 38.9%; trabeculectomy, 54.5%) and hypotony (IOP \u3c6 mm Hg at any time) (gel stent, 23.2%; trabeculectomy, 50.0%). CONCLUSIONS: At month 12, the gel stent was statistically noninferior to trabeculectomy, per the percentage of patients achieving ≥20% IOP reduction from baseline without medication increase, clinical hypotony, vision loss to counting fingers, or SSI. Trabeculectomy achieved a statistically lower mean IOP, numerically lower failure rate, and numerically lower need for supplemental medications. The gel stent resulted in fewer postoperative interventions, better visual recovery, and fewer AEs

Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression

OBJECTIVE: To investigate the rate of decline in forced vital capacity (FVC), and the effect of nintedanib on the rate of decline in FVC, in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who had risk factors for rapid decline in FVC. METHODS: The SENSCIS trial enrolled subjects with SSc and fibrotic ILD of ≥10% extent on high-resolution CT. The rate of decline in FVC over 52 weeks was analysed in all subjects and in those with early SSc (<18 months since first non-Raynaud symptom), elevated inflammatory markers (C reactive protein ≥6 mg/L and/or platelets ≥330×109/L) or significant skin fibrosis (modified Rodnan skin score (mRSS) 15-40 or mRSS ≥18) at baseline. RESULTS: In the placebo group, the rate of decline in FVC was numerically greater in subjects with <18 months since first non-Raynaud symptom (-167.8 mL/year), elevated inflammatory markers (-100.7 mL/year), mRSS 15-40 (-121.7 mL/year) or mRSS ≥18 (-131.7 mL/year) than in all subjects (-93.3 mL/year). Nintedanib reduced the rate of FVC decline across subgroups, with a numerically greater effect in patients with these risk factors for rapid FVC decline. CONCLUSION: In the SENSCIS trial, subjects with SSc-ILD who had early SSc, elevated inflammatory markers or extensive skin fibrosis had a more rapid decline in FVC over 52 weeks than the overall trial population. Nintedanib had a numerically greater effect in patients with these risk factors for rapid ILD progression

A Health-Related Quality of Life Measure for Patients Who Undergo Minimally Invasive Glaucoma Surgery

PurposeTo develop a patient-reported outcome measure to assess the impact of glaucoma and treatment, including minimally invasive glaucoma surgery (MIGS).DesignObservational study before and after concomitant cataract and Food and Drug Administration-approved implantable MIGS device surgery.SettingSurvey administration was on a computer, iPad, or similar device.Patient population184 adults completed the baseline survey, 124 a survey 3 months after surgery, and 106 the 1-month test-retest reliability survey. The age range was 37 to 89 (average age = 72). Most were female (57%), non-Hispanic White (81%), and had a college degree (56%).Main outcome measuresThe Glaucoma Outcomes Survey (GOS) assesses functional limitations (27 items), vision-related symptoms (7 items), psychosocial issues (7 items), and satisfaction with microinvasive glaucoma surgery (1 item). These multiple-item scales were scored on a 0 to 100 range, with a higher score indicating worse health.ResultsInternal consistency reliability estimates ranged from 0.75 to 0.93, and 1-month test-retest intraclass correlations ranged from 0.83 to 0.92 for the GOS scales. Product-moment correlations among the scales ranged from 0.56 to 0.60. Improvement in visual acuity in the study eye from baseline to the 3-month follow-up was significantly related to improvements in GOS functional limitations (r = 0.18, P = .0485), vision-related symptoms (r = 0.19, P = .0386), and psychosocial concerns (r = 0.18, P = .0503). Responders to treatment ranged from 17% for vision-related symptoms to 48% for functional limitations.ConclusionsThis study supports using the GOS for ophthalmic procedures such as MIGS. Further evaluation of the GOS in different patient subgroups and clinical settings is needed

Felony Murder and Capital Punishment: an Examination of the Deterrence Question

A proper test of the deterrent effect of the death penalty must consider capital homicides. However, the criterion variable in most investigations has been total homicides—most of which bear no legal or theoretical relationship to capital punishment. To address this fundamental data problem, this investigation used Federal Bureau of Investigation data for 1976–1987 to examine the relationship between capital punishment and felony murder, the most common type of capital homicide. We conducted time series analyses of monthly felony murder rates, the frequency of executions, and the amount and type of television coverage of executions over the period. The analyses revealed occasional departures (for vehicle theft and narcotics killings) from the null hypotheses. However, on balance, and in line with the vast majority of capital punishment studies, this investigation found no consistent evidence that executions and the television coverage they receive are associated significantly with rates for total, index, or different types of felony murder

Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma

Additional file 5: Table S5. of Collagen matrix vs mitomycin-C in trabeculectomy and combined phacoemulsification and trabeculectomy: a randomized controlled trial

Visual Field Mean Deviation. (DOCX 21 kb