Phase 3 Randomized Clinical Trial of the Safety and Efficacy of Travoprost Intraocular Implant in Patients with Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of 2 models of the travoprost intraocular implant (fast-eluting [FE] and slow-eluting [SE] types) from 1 of 2 phase 3 trials (the GC-010 trial). DESIGN: Multicenter, randomized, double-masked, sham-controlled, noninferiority trial. PARTICIPANTS: Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am, 10 am, and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am, 10 am, and 4 pm timepoints at baseline. METHODS: Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193). MAIN OUTCOME MEASURES: The primary outcome was mean change from baseline IOP in the study eye at 8 am and 10 am, at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs) and ophthalmic assessments. RESULTS: Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy end point was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 time points. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively. The most common AEs included iritis (FE implant, 0.5%; SE implant, 5.1%), ocular hyperemia (FE implant, 3.0%; SE implant, 2.6%), reduced visual acuity (FE implant, 1.0%; SE implant, 4.1%; timolol, 0.5%), and IOP increased (FE implant, 3.5%; SE implant, 2.6%; timolol, 2.1%). One serious study eye AE occurred (endophthalmitis). CONCLUSIONS: The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period after a single administration. The IOP-lowering efficacy in both implant groups was statistically and clinically noninferior to that in the timolol group, with a favorable safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Role of Selection Effects in the Contact Hypothesis: Results from a U.S. National Survey on Sexual Prejudice.

Empirical research has documented that contact with lesbians and gays is associated with more positive feelings toward and greater support for legal rights for them, but we know less about whether these effects extend to informal aspects of same-sex relationships, such as reactions to public displays of affection. Furthermore, many studies have assumed that contact influences levels of sexual prejudice; however, the possibility of selection effects, in which less sexually prejudiced people have contact, and more sexually prejudiced people do not, raises some doubts about this assumption. We used original data from a nationally representative sample of heterosexuals to determine whether those reporting contact with a lesbian, gay, bisexual, or transgender friend or relative exhibited less sexual prejudice toward lesbian and gay couples than those without contact. This study examined the effect of contact on attitudes toward formal rights and a relatively unexplored dimension, informal privileges. We estimated the effect of having contact using traditional (ordinary least squares regression) methods before accounting for selection effects using propensity score matching. After accounting for selection effects, we found no significant differences between the attitudes of those who had contact and those who did not, for either formal or informal measures. Thus, selection effects appeared to play a pivotal role in confounding the link between contact and sexual prejudice, and future studies should exercise caution in interpreting results that do not account for such selection effects.

Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication. METHODS: Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1-2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters. RESULTS: Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months. CONCLUSION: The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months. TRIAL REGISTRY: ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016.

Travoprost Intracameral Implant Demonstrates Superior IOP Lowering Versus Topical Prostaglandin Analog Monotherapy in Patients with Open-Angle Glaucoma or Ocular Hypertension.

INTRODUCTION: This study was conducted to analyze and compare the intraocular pressure (IOP) treatment effect of the slow-eluting (SE) travoprost intracameral implant to the IOP treatment effect of topical prostaglandin analog (PGA) monotherapy in a subgroup of subjects who were on pre-study PGA monotherapy prior to enrollment in the two pivotal phase 3 trials of the travoprost intracameral implant. METHODS: A combined study population of 133 subjects from two phase 3 trials, who were on topical PGA monotherapy at screening, subsequently underwent a washout period from their topical PGA, and then were randomized and administered an SE travoprost intracameral implant. The subjects were analyzed for the IOP treatment effects of the pre-study topical PGA monotherapy and the in-study SE travoprost intracameral implant. Paired t-tests were used to compare the difference in screening minus post-washout baseline IOP versus month 3 minus post-washout baseline IOP. The IOP-lowering efficacy in eyes administered an SE travoprost intracameral implant was compared to the IOP lowering in the same eyes while on a topical PGA monotherapy prior to study entry. RESULTS: Pre-study topical PGA monotherapy and the SE travoprost intracameral implant demonstrated IOP treatment effects of -5.76 mmHg and -7.07 mmHg, respectively. The IOP-lowering treatment effect was significantly greater by 1.31 mmHg for the SE travoprost intracameral implant relative to pre-study PGA monotherapy (95% confidence interval: -2.01, -0.60; P = 0.0003). CONCLUSIONS: The SE travoprost intracameral implant demonstrated superior IOP-lowering treatment effect versus pre-study topical PGA monotherapy with a superiority margin that was both statistically significant and clinically meaningful. The greater IOP reduction from baseline while on the SE implant versus pre-study topical PGA monotherapy may be a reflection of the optimized adherence and continuous elution of PGA therapy into the anterior chamber achieved with the SE travoprost intracameral implant. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT03519386 and NCT03868124.

Long-Term Safety and Efficacy Evaluation of Travoprost Intracameral Implant Based on Pooled Analyses from Two Phase III Trials.

AIM: The purpose of this study was to conduct and interpret a pooled 12-month analysis of two prospective, multi-center, randomized, double-masked, controlled trials designed to assess the efficacy and safety of the travoprost intracameral implant (slow-eluting [SE] implant in development as a new therapeutic and fast-eluting [FE] implant included for masking purposes) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: Subjects with OAG or OHT, on 0-3 intraocular pressure (IOP)-lowering medications, baseline unmedicated mean diurnal IOP of ≥ 21 mmHg, and IOP ≤ 36 mmHg at each baseline diurnal timepoint, received either a travoprost implant and twice-daily (BID) placebo eye drops or BID timolol 0.5% eye drops and a sham procedure. Subjects were followed through 12 months and assessed for IOP, reduction in topical IOP-lowering medications, and safety parameters including treatment-emergent adverse events (TEAEs). IOP at 8AM was prospectively collected at all study visits through 12 months and diurnal IOP, measured at 8AM, 10AM, and 4PM, was prospectively collected at baseline, day 10, week 6, and months 3 and 12. RESULTS: A total of 1150 subjects were randomized (385 FE implant, 380 SE implant, and 385 sham/timolol) across the two trials. Statistical non-inferiority to timolol and clinically relevant reductions in 8AM IOPs were demonstrated at month 12. In more detail, both implant groups demonstrated statistical non-inferiority to timolol and clinically relevant reductions from baseline in mean diurnal IOP at all visits over the 12-month evaluation period when diurnal IOP was collected. Additionally, both implant groups demonstrated robust treatment effect based on 8AM average IOP from day 10 through the specified visit which ranged from day 10 to month 12 from 6.9 to 8.5 mmHg in the FE implant group; 6.8 to 8.5 mmHg in the SE implant group; and 7.3 to 7.5 mmHg in the sham/timolol group. With regards to reduction in topical pharmacotherapy, at month 12, 77.6% of FE and 81.4% of SE implant eyes were completely free of all topical IOP-lowering medications and a significantly greater proportion of FE and SE implant eyes (89.9% and 93.0%) versus sham/timolol eyes (66.9%) were on the same or fewer topical IOP-lowering medications compared with pre-study (p <  0.0001). Furthermore, of subjects on topical IOP medications at screening, a significantly greater proportion of FE implant (80.2%) and SE implant (85.1%) eyes versus sham/timolol (22.8%) eyes were on fewer topical IOP-lowering medications at month 12 compared with pre-study (p <  0.0001). Lastly, of SE implant eyes on same or fewer topical IOP-lowering medications at month 12, the average through month 12 decreased by 0.9 medications, and of those SE implant eyes on fewer topical IOP-lowering medications compared with pre-study, the average through month 12 decreased by 1.4 medications. The most common TEAEs related to study treatment were hyperemia (conjunctival or ocular), iritis, and IOP increased. CONCLUSION: The travoprost intracameral implant demonstrated robust IOP-lowering efficacy that was sustained and statistically non-inferior to timolol over the entire 12 months, resulting in a significant reduction in topical IOP-lowering medication use, with the majority of SE implant eyes remaining completely free of all topical IOP-lowering medications. In addition, the implant demonstrated a favorable safety and tolerability profile based on this pooled 12-month analysis of two pivotal trials. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03519386 (registered May 09, 2018) and NCT03868124 (registered March 08, 2019).

Travoprost Intracameral Implant for Open-Angle Glaucoma or Ocular Hypertension: 12-Month Results of a Randomized, Double-Masked Trial.

INTRODUCTION: This prospective, multicenter, randomized, double-masked pivotal phase 3 trial evaluated the efficacy and safety of the travoprost intracameral SE-implant (slow-eluting implant, the intended commercial product) and FE-implant (fast-eluting implant, included primarily for masking purposes) compared to twice-daily (BID) timolol ophthalmic solution, 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: The trial enrolled adult patients with OAG or OHT with an unmedicated mean diurnal intraocular pressure (IOP) of ≥ 21 and unmedicated IOP ≤ 36 mmHg at each diurnal timepoint (8 A.M., 10 A.M., and 4 P.M.) at baseline. The eligible eye of each patient was administered an SE-implant, an FE-implant or had a sham administration procedure. Patients who received an implant were provided placebo eye drops to be administered BID and patients who had the sham procedure were provided timolol eye drops to be administered BID. The primary efficacy endpoint, for which the study was powered, was mean change from baseline IOP at 8 A.M. and 10 A.M. at day 10, week 6, and month 3. Non-inferiority was achieved if the upper 95% confidence interval (CI) on the difference in IOP change from baseline (implant minus timolol) was < 1.5 mmHg at all six timepoints and < 1 mmHg at three or more timepoints. The key secondary endpoint was mean change from baseline IOP at 8 A.M. and 10 A.M. at month 12. Non-inferiority at month 12 was achieved if the upper 95% CI was < 1.5 mmHg at both timepoints. Safety outcomes included treatment-emergent adverse events (TEAEs) and ophthalmic assessments. RESULTS: A total of 590 patients were enrolled at 45 sites and randomized to one of three treatment groups: 197 SE-implant (the intended commercial product), 200 FE-implant, and 193 timolol. The SE-implant was non-inferior to timolol eye drops in IOP lowering over the first 3 months, and was also non-inferior to timolol at months 6, 9, and 12. The FE-implant was non-inferior to timolol over the first 3 months, and also at months 6 and 9. Of those patients who were on glaucoma medication at screening, a significantly greater proportion of patients in the SE- and FE-implant groups (83.5% and 78.7%, respectively) compared to the timolol group (23.9%) were on fewer topical glaucoma medications at month 12 compared to screening (P < 0.0001, chi-square test). TEAEs, mostly mild, were reported in the study eyes of 39.5% of patients in the SE-implant group, 34.0% of patients in the FE-implant group and 20.1% of patients in the timolol group. CONCLUSIONS: The SE-travoprost intracameral implant demonstrated non-inferiority to timolol over 12 months whereas the FE-implant demonstrated non-inferiority over 9 months. Both implant models were safe and effective in IOP lowering in patients with OAG or OHT. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03519386.

Not All Homes Are Safe: Family Violence Following the Onset of the Covid-19 Pandemic.

Evidence from victim service providers suggests the COVID-19 pandemic led to an increase in family violence. However, empirical evidence has been limited. This study uses novel survey data to investigate the occurrence of family violence during the early months of the COVID-19 pandemic in the United States. Data come from the second wave of the Assessing the Social Consequences of COVID-19 study, an online non-probability sample collected in April and May 2020. Family violence is measured using four variables: any violence, physical violence, verbal abuse, and restricted access. The authors use logistic regression and KHB decomposition to examine the prevalence of family violence during the COVID-19 pandemic. We find that sexual minorities, in particular bisexual people, experienced higher rates of family violence than heterosexual respondents. Women were the only group to report an increase in the frequency of family violence. Household income loss is associated with the incidence of verbal violence. Our findings demonstrate the importance of expanding victim services to address the additional barriers victims face within the pandemic context and beyond, including broad contexts of social isolation and financial precarity experienced by individuals at risk of family violence.

ModAsian FINDRISC as a Screening Tool for People with Undiagnosed Type 2 Diabetes Mellitus in Vietnam: A Community-Based Cross-Sectional Study.

Purpose: Our study aims to evaluate the risk of developing type 2 diabetes mellitus in the next 10 years using ModAsian FINDRISC and additionally explore associated factors among the Vietnam population. Participants and Methods: A cross-sectional study was conducted on 2258 participants aged 25 years old or above in Thua Thien Hue Province, Vietnam. The sample size is calculated based on the estimated sensitivity, and participants were randomly selected from different geographical and socio-economic areas. All participants were thoroughly medically examined, taking blood lipid profile and fasting blood glucose, taking blood pressure, anthropometric indexes, 12-lead electrocardiogram, and behavioral factors were investigated using the Vietnamese version of the WHO STEPS toolkit. The risk of developing T2DM was made based on the ModAsian FINDRISC. Results: The incidence of developing type 2 diabetes mellitus among the study population was 4.21%. The group with a high or very high risk of developing type 2 diabetes mellitus in the next 10 years accounted for 2.52%. Body mass index (AUC = 0.840, 95% CI: 0.792-0.888), waist circumference (AUC = 0.824, 95% CI: 0.777-0.871), family history of diabetes mellitus (AUC = 0.751, 95% CI = 0.668-0.833), and history of antihypertensive medication use regularly (AUC = 0.708, 95% CI: 0.632-0.784) are the most associated factors of the ModAsian FINDRISC. Residential location (OR = 5.62, 95% CI: 1.91-16.54) and occupational status (OR = 0.35, 95% CI: 0.20-0.62) were significant factors associated with a high and very high risk of developing type 2 diabetes mellitus in the next 10 year. Conclusion: Screening for the risk of type 2 diabetes mellitus and implementing intervention programs focusing on controlling weight, waist circumference, and blood pressure are essential for reducing type 2 diabetes mellitus incidence and burden in Vietnam.

Changes in Mental Health and Well-Being Are Associated With Living Arrangements With Parents During COVID-19 Among Sexual Minority Young Persons in the U.S.

Sexual minority young persons may be at risk for compounding mental health effects of the COVID-19 pandemic due to their existing vulnerabilities for psychological inequities. Indeed, recent research has documented that sexual minority young persons are experiencing compounding psychiatric effects associated with the COVID-19 pandemic. Further, researchers and practitioners hypothesized that sexual minority youth and young adults may experience unique hardships related to their sexual and gender identities and familial conflict as a result of the COVID-19 pandemic and living arrangement changes with their parents and families. This study aims to investigate whether there are changes in sexual minority (and non-sexual minority) young adults' (SMYAs) mental health and wellbeing among those living with and living without their parents before and after the start of COVID-19. Among a cross-sectional sample of SMYAs (n=294; Mage=22 years; age range=18-26) and non-SMYAs (n=874; Mage=22 years; age range=18-26) defined by whether they were living with or living without their parents before and after the start of COVID-19, we retrospectively analyzed changes in psychological distress and wellbeing. SMYAs who returned to their parents' homes during post-onset of COVID-19 reported greater mental distress and lower wellbeing, followed by those who were living with their parents both before and after the start of COVID-19. Patterns were not consistent among non-SMYAs, and lower magnitudes of change were seen. There is a significant public health need for mental health services and family education resources for supporting SMYAs in the context of COVID-19 and beyond.

Blurred border or safe harbor? Emotional well-being among sexual and gender minority adults working from home during COVID-19.

During the COVID-19 pandemic, lesbian, gay, bisexual, transgender, and queer (LGBTQ) adults have experienced pronounced declines in well-being. However, less is known about how changes to daily routines and settings, such as the shift to remote work within many occupations, may be playing a role in well-being outcomes. Drawing on a unique time diary data source (N = 3515 respondents and 7650 episodes) collected between April 2020-July 2021 through online crowdsourcing platforms, we conducted random effects analyses to examine how working from home has been associated with experienced well-being among LGBTQ and cisgender heterosexual workers in the United States during the pandemic. Findings indicate LGBTQ adults felt significantly less stressed and tired while doing paid work at home than while working at a workplace. In addition, working at a workplace, rather than working from home, appeared to be more detrimental to LGBTQ adults' well-being compared to their non-LGBTQ counterparts. Adjusting for work characteristics explained some of the difference, whereas adjusting for family characteristics had little impact on the results. It is possible that for LGBTQ employees, working from home mitigates some of the minority stressors experienced during paid work.

Mothering and Stress during COVID-19: Exploring the Moderating Effects of Employment.

Using primary data from the Assessing the Social Consequences of COVID-19 study, the authors examined how the pandemic affected the stress levels of women with and without coresiding minor children (mothers vs. nonmothers), paying special attention to the moderating role of employment status. The ordinary least squares regression results show that following the pandemic outbreak, among full-time working women, mothers reported smaller stress increases than nonmothers. In contrast, among part-time and nonemployed women, mothers and nonmothers experienced similar stress increases. Also, full-time working mothers reported smaller stress increases than women with most other mothering and employment statuses. Changes in women's employment status, following pandemic onset, had limited impacts on the patterns of stress change. This study contributes to research on parenting and health by showing that during times of crisis, full-time employment may be protective of mothers' mental health but may not buffer the mental health deterioration of women not raising children.

Sexual Minority Disparities in Health and Well-Being as a Consequence of the COVID-19 Pandemic Differ by Sexual Identity.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has accentuated long-standing population health disparities in the United States. We examined how the pandemic and its social consequences may differentially impact sexual minority adults, relative to heterosexual adults. Methods: Data are from a U.S. national sample of adults (n = 2996; 18.06%) collected from online panels from April to May 2020. We used eight indicators of well-being-mental health, physical health, quality of life, stress, loneliness, psychological distress, alcohol use, and fatigue-to assess the degree to which sexual identity subgroups (i.e., heterosexual, gay/lesbian, bisexual, and "other" sexual minority) varied in retrospective pre- and postpandemic onset indicators of well-being and whether groups varied in their rate of change from pre- and postpandemic onset. Results: The results showed consistent patterns of decline in well-being across sexual identity subgroups, although changes in mental health, physical health, quality of life, stress, and psychological distress were more robust among sexual minority adults in general, relative to heterosexual adults. Adjusted multivariate models testing differences in change in retrospective pre- and postpandemic onset found that well-being among bisexual men and women was most negatively impacted by the pandemic. Conclusion: The COVID-19 pandemic may have distinct health consequences for sexual minority adults in the United States. Our findings support and further legitimize calls for more comprehensive surveillance and cultural responsiveness in emergency preparedness as it relates to sexual minority people and the COVID-19 pandemic.