Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients With Wet Age-Related Macular Degeneration.

Purpose: To evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan-VEGF receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy. Design: Phase I, multicenter, prospective, open-label, dose-escalation trial. Participants: Patients with wAMD and evidence of prior anti-VEGF therapy response. Methods: Patients received a single intravitreal injection of EYP-1901. Main Outcome Measures: The primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates. Results: Seventeen patients enrolled in the 440 µg (3 patients), 1030 µg (1 patient), 2060 µg (8 patients), and 3090 µg (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline in BCVA was -1.8 letters and -5.4 letters at 6 and 12 months. Mean change from baseline in CST was +1.7 µm and +2.4 µm at 6 and 12 months. Reduction in treatment burden was 74% and 71% at 6 and 12 months. Of 16 study eyes, 13, 8, and 5 were injection-free up to 3, 6, and 12 months. Conclusion: In the DAVIO trial (ClinicalTrials.gov identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing phase II and planned phase III trials to assess efficacy and safety. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Alcohol-Related Problems As Moderators of PTSD Symptom Change During Use of a Web-Based Intervention for Hazardous Drinking and PTSD.

OBJECTIVE: Alcohol-related problems (e.g., physical, interpersonal, intrapersonal, impulse control, social responsibility) can have an impact on posttraumatic stress disorder (PTSD) symptoms during treatment. Evidence-based online self-help tools exist to target alcohol use and related problems and co-occurring PTSD symptoms. It is unknown to what degree individuals with varying alcohol-related problems respond differently to web-based interventions for hazardous alcohol use and PTSD. The current study evaluated specific alcohol-related problems as potential moderators of PTSD symptom changes during the VetChange online intervention while controlling for average daily alcohol use, gender, race, and age. METHOD: We conducted a secondary analysis of a randomized controlled trial that included 600 post-9/11 veterans (518 men and 82 women). Mixed-effects regression models of alcohol-related problems on PTSD severity scores over time were performed separately in an initial intervention group (IIG; n = 404) and a delayed intervention group (DIG; n = 196) that was used as a comparison condition. RESULTS: Interpersonal problems emerged as a moderator of PTSD symptom changes in IIG such that veterans endorsing greater interpersonal problems demonstrated larger reductions in PTSD symptoms throughout VetChange. There were no significant moderation effects in DIG. Non-White veterans reported significantly higher PTSD symptoms during VetChange. Post hoc analyses indicated that veterans with higher interpersonal problems were more likely to engage in online intervention content focused on identifying high-risk drinking situations and coping with symptoms. CONCLUSIONS: Findings imply that veterans reporting alcohol-related interpersonal problems may benefit the most from, and be more motivated to use, online interventions for hazardous alcohol use and PTSD symptoms.

Parkinson's Disease, Impulsive-Compulsive Behaviors, and Health-Related Quality of Life.

OBJECTIVE: A large body of literature has examined the links between the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) and the development of "impulsive-compulsive behaviors (ICBs)." Little is known regarding the link between the development of ICBs and health-related quality of life (HRQOL). We aimed to explore the factors that are associated with poorer HRQOL, especially in relation to DRT-induced ICBs, in a sample of PD patients. METHODS: This PARKADD (PARK: PARKinson's disease; ADD: behavioral ADDictions) study was a prospective case‒control study initially designed to assess the factors associated with ICBs in PD patients. A prospective clinical follow-up was added, aiming to capture the long-term evolution of HRQOL in relation to ICBs occurring or worsening after the beginning of PD. We focused on sociodemographic and PD characteristics and the history or presence of ICBs. HRQOL was measured using the Parkinson's Disease Questionnaire-8. A multivariate linear regression was performed to identify factors related to poorer HRQOL. RESULTS: A total of 169 patients were eligible for the follow-up study. The presence of an ICB, a higher levodopa equivalent daily dose (LEDD) and a longer PD duration were significantly associated with poorer HRQOL, with an interaction between LEDD and PD duration. CONCLUSION: The presence of an ICB was related to poorer HRQOL and should be considered a crucial factor for the management of PD patients. Several studies were recently published that provide guidelines for the management of these patients, with recommendations based on two key principles: prevention and specific treatment.

Network analysis of reasons for and against changing alcohol use among veterans engaged in a web-based intervention for hazardous drinking and PTSD symptoms.

Better understanding of reasons for and against change may be an effective strategy for supporting drinking reduction or abstinence among Iraq and Afghanistan veterans. The current study explored connections between reasons for and against changing hazardous alcohol use, as well as the relative importance of a given reason. Data from 366 veterans (86% male, 77% White) between the ages of 21 and 56 (M = 31.8, SD = 7.3) were obtained from a nationwide web-based alcohol and posttraumatic stress disorder randomized clinical trial. Participant-generated reasons for and against change were used to estimate two separate network models. The network of motives for changing alcohol use was generally well connected with predominately positive associations. Veterans reporting motivation to change alcohol use to improve functioning, enhance self-worth, and decrease alcohol-related consequences tended to have higher than average motivation to reduce or abstain from alcohol use. Alternatively, the network structure of motives against changing alcohol use demonstrated a nearly equal number of positive and negative associations. Whereas reasons to cope and sleep may imply higher than average motivation to continue drinking the same, veterans reporting reasons to reduce anxiety and have fun tended to have lower than average motivation to continue drinking. The current study may inform content modifications to self-help tools to more quickly and effectively target users' motivations from the beginning. Capitalizing on intervention users' motivations early may promote sustained engagement or improve therapeutic impact among those who only use the intervention for a short period of time.

Life satisfaction following treatment-related reductions in alcohol use and PTSD symptoms: Results from VetChange.

OBJECTIVE: Rates of hazardous alcohol consumption and co-occurring posttraumatic stress disorder (PTSD) are high among returning combat veterans and may adversely affect satisfaction with life (SWL). Improving life satisfaction represents a potential secondary outcome of web-based interventions for alcohol use and PTSD. Understanding the relationship between intervention targets and SWL may help inform future interventions and provide clarity regarding how improvements are manifesting. We examined returning veterans enrolled in VetChange, an evidence-based web intervention for co-occurring alcohol use and PTSD, to determine changes in SWL over time and as a function of changes in alcohol consumption and PTSD symptoms. METHOD: Participants included 222 returning veterans who reported hazardous drinking. Veterans engaged in a nationwide implementation of VetChange and completed measures of average weekly drinks (AWD), PTSD symptoms, and SWL at baseline, 1, 3, and 6 months. We investigated the effects of changes in PTSD and AWD between baseline and 1 month on SWL over 6 months using linear mixed-effects modeling. RESULTS: Across all veterans, SWL increased by 19% over 6 months. AWD and PTSD decreased between baseline and 1 month, but only change in PTSD predicted changes in SWL over the 6-month interval. CONCLUSIONS: Reductions in PTSD symptoms within the first month of intervention use, and not reductions in drinking, predicted increased SWL over 6 months. SWL is an important marker for recovery and related quality of life, and an important assessment and intervention target of web-based interventions. Interventions may also target SWL, as improvements in SWL promote future recovery and sustained improvement. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Parkinson's disease and iatrogenic impulsive-compulsive behaviors: A case/non-case study to build a complete model of individual vulnerability.

Background and aims: Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. First-line medications consist of drugs that act by counteracting dopamine deficiency in the basal ganglia. Unfortunately, iatrogenic impulsive-compulsive behaviors (ICBs) can occur in up to 20% of PD patients over the course of their illness. ICBs must be considered multifactorial disorders that reflect the interactions of the medication with an individual's vulnerability and the underlying neurobiology of PD. We aimed to explore the predictive genetic, psychopathological and neurological factors involved in the development of ICBs in PD patients by building a complete model of individual vulnerability. Methods: The PARKADD study was a case/non-case study. A total of 225 patients were enrolled ("ICB" group, N = 75; "no ICB" group, N = 150), and 163 agreed to provide saliva samples for genetic analysis. Sociodemographic, neurological and psychiatric characteristics were assessed, and genotyping for the characterization of polymorphisms related to dopaminergic and opioid systems was performed. Results: Factors associated with "ICBs" were younger age of PD onset, personal history of ICB prior to PD onset and higher scores on the urgency and sensation seeking facets of impulsivity. No gene variant was significantly associated, but the association with the opioid receptor mu 1 (OPRM1) rs1799971 polymorphism was close to significance. Discussion and conclusions: The influence of gene-environment interactions probably exists, and additional studies are needed to decipher the possible role of the opioid system in the development of ICBs in PD patients.

Psychosocial Features of Shift Work Disorder.

To better understand Shift Work Disorder (SWD), this study investigates insomnia, sleepiness, and psychosocial features of night workers. The study compares night workers with or without SWD to day workers with or without insomnia. Seventy-nine night workers and 40 day workers underwent diagnostic interviews for sleep disorders and for psychopathologies. They completed questionnaires and a sleep diary for 14 days. The design was observatory upon two factors: Work schedule (night, day work) and sleep (good sleep, SWD/insomnia). Two-way ANCOVAs were conducted on psychosocial variables, and effect size were calculated. The clinical approach chosen led to distinct groups of workers. Night workers slept several periods (main sleep period after work, naps, nights on days off). High total wake time and low total sleep time characterized sleep in SWD. Most night workers with SWD still complained of sleepiness after main sleep. Cognitive activation distinguished groups of night workers. All other differences in psychosocial variables between night workers groups were similar to, but smaller than, the ones between day workers. The evaluation of SWD should consider all sleep periods of night workers with particular attention to self-reported total wake time, state sleepiness, and level of cognitive activation.

Differential alcohol treatment response by gender following use of VetChange.

OBJECTIVE: Proportionally more women use online alcohol interventions but also report less robust treatment outcomes compared to men. Less is known about outcome disparities among veteran women, who are a growing demographic nationally. The current study examined gender differences among returning veteran men and women who used VetChange, a web-based intervention for hazardous drinking and posttraumatic stress symptoms (PTSS). METHOD: Using data from a nationwide implementation study of returning combat veterans (n = 222), we performed hierarchical linear modeling to examine gender differences in alcohol and PTSS outcomes over six months following VetChange registration. Additional analyses examined gender differences in proportional changes in hazardous drinking and at each assessment point. RESULTS: Returning veterans reported significant decreases in alcohol use and PTSS over time, yet men evidenced significantly greater reduction in average weekly drinks and drinks per drinking day compared to women. Follow up analyses indicated that women were significantly less likely than men to achieve low-risk drinking by one month post-registration. Proportional change in alcohol use yielded marginal and non-significant trends that were, nonetheless, consistent with the overall pattern of gender differences. CONCLUSION: These results contribute to emerging literature suggesting that women use online alcohol use interventions at proportionately higher rates than do men, but do not reduce their drinking as much as men. There are a number of potential content changes that could improve outcomes for returning veteran women using online interventions, and data-driven adaptations based on stakeholder input are recommended.

Public implementation of a web-based program for veterans with risky alcohol use and PTSD: A RE-AIM evaluation of VetChange.

BACKGROUND: Evidence-based web and mobile interventions are available for a range of mental health concerns. Little is known about how self-administered web interventions are used outside of controlled research trials, and there is a critical need to empirically examine real-world public implementation of such programs. To this end, the aim of the current study was to evaluate and describe outcomes of a nationwide public implementation of VetChange, a self-administered web intervention for veterans with problematic alcohol use and symptoms of PTSD. METHOD: The study used the RE-AIM framework to organize outcomes along five key dimensions: reach, effectiveness, adoption, implementation, and maintenance. This naturalistic observation study included program use information for all who registered an account with VetChange during the 2-year study period and who self-identified as a returning veteran. We collected program use data automatically via normal website operation; a subset of program users provided additional self-report outcome data. The study used linear multilevel mixed modeling to evaluate changes in alcohol use and PTSD symptoms over a six-month postregistration period. RESULTS: VetChange successfully reached a large, geographically diverse sample of returning veterans with risky drinking and PTSD symptoms. Despite variable, overall modest, rates of intervention use over time, registered users demonstrated significant improvements in drinking, PTSD, and quality of life, and participants maintained these outcomes at a six-month follow-up. CONCLUSIONS: Given the observed low cost per acquisition, positive clinical outcomes, and the potential to produce long-term cost savings through reduced health care burden associated with chronic alcohol use disorder and PTSD, this study demonstrates how web-based interventions can provide public health benefits and reduce long-term health care costs.

Understanding motives for and against hazardous drinking and change among returning veterans.

The prevalence of hazardous drinking is elevated among returning veterans of Iraq and Afghanistan wars, particularly among returning veterans and those with co-occurring posttraumatic stress disorder (PTSD) symptoms. Understanding the reasons for drinking as well as motivations for change can tremendously improve intervention efforts. Unfortunately, little is currently known regarding the motivations that might facilitate or hinder change among returning veterans. In the current study, we examined returning veterans' reasons to change or not change drinking through analysis of responses to an open-ended decisional balance exercise. We included 366 returning veterans selected from a larger sample of returning veterans enrolled in a web-based randomized-controlled trial of an online intervention for alcohol use and PTSD. We used qualitative content analysis to systematically classify responses into categories through identification of common themes. Top reasons to change/reduce drinking included reducing negative physical effects, improve finances, and expected social/interpersonal benefits of reduction or abstaining. Top reasons to continue drinking/not change included facilitation of social interaction, promote sleep, and reduce tension. The current study adds to our phenomenological understanding of motivations for and against changing drinking among returning veterans. Whereas many motives were consistent with those of nonveteran samples, others appear to distinguish, and are uniquely salient among, returning veterans (e.g., to manage sleep and PTSD symptoms). These results provide insight into key assessment and intervention points regarding hazardous drinking among returning veterans. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Are cognitive variables that maintain insomnia also involved in shift work disorder?

OBJECTIVE: Shift Work Disorder (SWD) is explained mainly by a misalignment between the sleep schedule and the circadian rhythm. However, the possible role of cognitive variables in maintaining SWD remains unknown. Therefore, the objective of this study is to evaluate whether cognitive variables known to maintain insomnia in day workers might also be involved in perpetuating SWD. DESIGN: Cross-sectional. SETTING: Sleep laboratory. PARTICIPANTS: Twenty-five shift workers diagnosed with SWD (84% females; mean age = 35.9) and 22 shift workers who are good sleepers (91% females; mean age = 34.1). MEASUREMENTS: The participants completed a sleep diary for two weeks, answered questionnaires, and underwent the Harvey's semistructured interview and the catastrophizing procedure. Data from the catastrophizing procedure underwent a content analysis. RESULTS: Compared with good sleepers, shift workers with SWD reported experiencing more thoughts that keep them awake, more presleep cognitive arousal, more dysfunctional beliefs related to worries and helplessness, and more selective attention toward worries and noises. However, the two groups did not differ on the tendency to catastrophize about difficulties falling asleep. Furthermore, 12 catastrophizing themes were identified in the entire sample, the most frequently endorsed being "sleepiness and energy" and "performance at work." CONCLUSIONS: The results suggest that cognitive variables may play a role in maintaining SWD. Finally, worries that interfere with sleep in shift workers are related to their work context.

Changes in alcohol use, PTSD hyperarousal symptoms, and intervention dropout following veterans' use of VetChange.

OBJECTIVE: Veterans of Iraq and Afghanistan conflicts report high rates of drinking, PTSD, and low rates of treatment engagement. Web interventions may help address unmet treatment need; unfortunately, little is known regarding outcomes or adherence to these interventions. In this study, we examined VetChange treatment outcomes and downstream effects of alcohol reduction on PTSD symptoms and intervention dropout rates over six months. METHOD: Participants included 222 veterans (77.5% men, 78.3% White) between 22 and 57 (mean age = 36.02, SD = 7.19). All VetChange users completed a brief alcohol assessment and received personal feedback, then received full access to intervention content including psychoeducation; motivational and cognitive-behavioral modules for relapse prevention, goal-setting, social support, stress, anger, and sleep management; and mood and drink tracking. Veterans completed self-report measures of alcohol use and PTSD symptoms at baseline, one, three, and six months. RESULTS: Alcohol use dropped by 43% over six months, p < .001, with the largest decrease occurring within the first month. Greater alcohol reduction in the first month predicted higher subsequent PTSD hyperarousal severity. Over half (52.3%) dropped out by month one, followed by 12.2% and 37.6% by months three and six. Hyperarousal symptoms, hypervigilance specifically, but not alcohol use predicted subsequent intervention dropout. CONCLUSION: These results highlight the importance of attending to the association between alcohol use and PTSD symptom change in web-based interventions for veterans. The fact that hyperarousal symptoms were associated with elevated risk for intervention dropout signifies the need for online intervention refinement aimed at tailoring content to time-varying symptom presentations.

MT in anticoagulated patients: Direct oral anticoagulants versus vitamin K antagonists.

Mechanical thrombectomy (MT) is one of the main treatments for acute ischemic stroke (AIS) in patients on effective anticoagulation. The use of direct oral anticoagulants (DOA) has increased, given their efficacy and safety profile compared to vitamin K antagonists (VKA). We compared procedural and clinical outcomes of MT in patients on DOA and VKA treatment before stroke onset. We analyzed 2 groups from the Endovascular Treatment in Ischemic Stroke prospective registry: patients on DOA and patients on VKA treated by MT without thrombolysis. Generalized linear mixed models including center as random effect were used to compare angiographic (rates of reperfusion at end of procedure, number of passes >2, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to anticoagulation subgroups. Comparisons were adjusted for prespecified confounders (age, admission NIH Stroke Scale score) as well as for meaningful baseline between-group differences. Among 221 patients included, more DOA-treated patients (n = 115, 52%) achieved successful (modified Thrombolysis in Cerebral Infarction score [mTICI] 2b/3) or near complete (mTICI 2c/3) reperfusion at the procedure end than did VKA-treated patients, with an adjusted odds ratio (OR) for DOA vs VKA of 3.27 (95% confidence interval [CI], 1.40-7.65) and 2.00 (95% CI, 1.08-3.73), respectively. DOA-treated patients had a lower 90-day mortality risk with an adjusted OR of 0.47 (95% CI, 0.24-0.89) and a better excellent outcome OR of 2.40 (1.10-5.27). There was no significant between-group difference in hemorrhagic or procedural complications. The study highlights the benefits of DOA compared to VKA. Regarding mortality, excellent outcomes, and recanalization rate, DOA appears to provide a favorable setting for MT treatment in AIS.

Ocular comfort assessment of lifitegrast ophthalmic solution 5.0% in OPUS-3, a Phase III randomized controlled trial.

PURPOSE: To evaluate ocular comfort of lifitegrast ophthalmic solution 5.0% among patients with dry eye disease (DED) in the OPUS-3 trial. METHODS: OPUS-3 was a multicenter, randomized, double-masked, placebo-controlled study. Adults with DED and recent artificial tear use were randomized 1:1 (lifitegrast:placebo) to ophthalmic drops twice daily for 84 days. On days 0 (baseline), 14, 42, and 84, drop comfort score (scale, 0-10; 0 = very comfortable, 10 = very uncomfortable) was measured at 0, 1, 2, and 3 minutes postinstillation. If the score was >3 at 3 minutes, assessment was repeated at 5, 10, and 15 minutes until score ≤3. Ocular treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Overall, 711 participants were randomized (n=357 received lifitegrast; n=354 received placebo). Drop comfort scores for lifitegrast-treated participants improved within 3 minutes of instillation (mean scores on day 84 for both study and fellow eyes: instillation: lifitegrast, 3.4, placebo, 1.0; 3 minutes: lifitegrast, 1.5, placebo, 0.7). The majority (64%-66%) of participants had scores <3 within 3 minutes postinstillation on days 14, 42, and 84. In participants with scores >3 at 3 minutes, the mean score in the lifitegrast group was similar to or better than that in the placebo group at 5, 10, or 15 minutes postinstillation. Lifitegrast appeared to be well tolerated, with ocular TEAEs rarely leading to discontinuation. CONCLUSION: In OPUS-3, lifitegrast appeared to be well tolerated and drop comfort scores approached placebo levels by 3 minutes postinstillation.

Web-based alcohol intervention for veterans: PTSD, combat exposure, and alcohol outcomes.

OBJECTIVE: The purpose of the current study was to evaluate the relationship between baseline levels of posttraumatic stress disorder (PTSD), combat exposure, and alcohol outcomes in a sample of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans using a web-based self-management intervention (VetChange) for problem drinking. METHOD: The current study focuses on 523 veterans who participated in a larger randomized clinical trial. Analyses in the current study include (a) multivariable linear regression models to assess the relationship between PTSD, combat exposure, and alcohol variables at baseline, and (b) general linear models accounting for correlated data within subjects to analyze change over time for alcohol outcomes as a function of baseline PTSD symptoms, combat exposure, and covariates. RESULTS: There was a positive association between PTSD symptom severity and alcohol use and alcohol problem severity at baseline. However, participants with higher baseline PTSD symptoms demonstrated a significantly greater reduction in alcohol use during the intervention and a greater reduction in alcohol problems from baseline to 3-month follow-up. Combat exposure severity was positively associated with alcohol problems at baseline. However, veterans with higher exposure demonstrated a greater reduction in average weekly drinking between end of intervention and follow-up, and otherwise showed changes similar to participants with lower exposure. CONCLUSIONS: Higher levels of baseline PTSD symptoms and combat exposure severity did not prevent OEF/OIF veterans from achieving positive alcohol outcomes through participation in a self-management web intervention for problem drinking. (PsycINFO Database Record

Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3).

PURPOSE: Lifitegrast is a lymphocyte function-associated antigen-1 antagonist developed to reduce inflammation in dry eye disease (DED). We report the results of OPUS-3 (NCT02284516), a phase III study evaluating the efficacy and safety of lifitegrast versus placebo in participants with DED. DESIGN: Twelve-week, phase III, randomized, double-masked, multicenter, placebo-controlled study. PARTICIPANTS: Adults aged ≥18 years with Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, corneal fluorescein staining score ≥2.0 (0-4 scale), eye dryness score (EDS) ≥40 (0-100 visual analogue scale [VAS]), and history of artificial tear use within 30 days of study entry. METHODS: After a 14-day placebo run-in, participants were randomized 1:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. MAIN OUTCOME MEASURES: The primary efficacy end point was change from baseline to day 84 in EDS. Key secondary efficacy end points were change from baseline to days 42 and 14 in EDS. Other secondary efficacy end points included additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain), ocular discomfort score (ODS), and safety/tolerability of lifitegrast versus placebo. RESULTS: In the study, 711 participants were randomized: placebo, 356; lifitegrast, 355 (intention-to-treat [ITT] population). At day 84, lifitegrast-treated participants experienced significantly greater improvement from baseline in EDS versus those receiving placebo (treatment effect [TE], 7.16; 95% confidence interval [CI], 3.04-11.28; P = 0.0007). Mean changes from baseline in EDS also significantly favored lifitegrast on days 42 (TE, 9.32; 95% CI, 5.44-13.20; P < 0.0001) and 14 (TE, 7.85; 95% CI, 4.33-11.37; P < 0.0001). No statistically significant differences were observed in ODS between treatment groups at days 84, 42, or 14. A greater improvement was observed in lifitegrast-treated participants at day 42 in itching (nominal P = 0.0318), foreign body sensation (nominal P = 0.0418), and eye discomfort (P = 0.0048) versus participants receiving placebo. Most treatment-emergent adverse events were mild to moderate in severity; no serious ocular adverse events were reported. CONCLUSIONS: Lifitegrast significantly improved symptoms of eye dryness, as measured by EDS, versus placebo in participants with DED. Improvement in EDS was observed as early as day 14. Lifitegrast appeared well tolerated.

Serum Phenobarbitone Levels in Term and Near Term Neonates with Seizures.

OBJECTIVE: To evaluate serum phenobarbitone levels in neonates with seizures and to evaluate the effect of repeated loading dose on serum phenobarbitone levels. METHODS: In this prospective observational study conducted in a tertiary care centre of Northern India during 2011- 2012, 99 neonates admitted with seizureswere included.Serum phenobarbitone levels in neonates with seizures at 20 minutes and 12 hours after the first loading dose of phenobarbitone were measured. RESULTS: Serum phenobarbitone levels [mean (SD)] at 20 min and 12 hours was 27.3 (28.4) ug/mL and 23 (19.1) ug/mL, respectively (P=0.07). The mean serum phenobarbitone levels 12 hours after the loading dose, and proportion of neonates with toxic levels increased with each loading dose of intravenous phenobarbitone. CONCLUSION: Monitoring of serum level of phonobarbitone may not be essential because seizure control in neonates appears to be independent of whether serum level is subtherapeutic, therapeutic or toxic range.

Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease: A 1-Year, Multicenter, Randomized, Placebo-Controlled Study.

PURPOSE: To evaluate the 1-year safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease compared with placebo. METHODS: SONATA (Safety Of a 5.0% coNcentrATion of lifitegrAst ophthalmic solution) was a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 study (NCT01636206). Adults (≥18 years) with dry eye disease (Schirmer test score ≥1 and ≤10 mm; corneal staining score ≥2.0) were randomized 2:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 360 days. The primary objective was percentage and severity of treatment-emergent adverse events (TEAEs). Secondary objectives were ocular safety measures: corneal fluorescein staining, drop comfort, best-corrected visual acuity, slit-lamp biomicroscopy, and intraocular pressure over 7 visits. Exploratory objectives included concentration of lifitegrast in plasma. RESULTS: The safety population comprised 331 participants (220 lifitegrast; 111 placebo). There were no serious ocular TEAEs. Overall, 53.6% of participants receiving lifitegrast experienced ≥1 ocular TEAE versus 34.2% in the placebo group; most TEAEs were mild to moderate in severity. Rates of discontinuation because of TEAEs were 12.3% (lifitegrast) versus 9.0% (placebo). The most common (>5%) TEAEs occurring in either treatment group were instillation site irritation (burning), instillation site reaction, visual acuity reduced, dry eye, and dysgeusia (change in taste). Ocular safety parameters for lifitegrast were similar to placebo. The mean plasma lifitegrast concentration at 360 days (n = 43) was below the limit of detection. There was no indication of systemic toxicity or localized infectious complications secondary to chronic immunosuppression. CONCLUSIONS: Lifitegrast ophthalmic solution 5.0% seemed safe and well tolerated in this study, with no unexpected adverse events.

Drinking goal choice and outcomes in a Web-based alcohol intervention: results from VetChange.

OBJECTIVES: The objectives of the paper are to describe characteristics of participants who chose moderation and abstinence drinking goals, and to examine post-treatment drinking outcomes based on patterns of goal choice during a Web-based alcohol intervention for returning U.S. Veterans. METHOD: We conducted a descriptive secondary analysis of a subsample of 305 of 600 Veterans who participated in a clinical trial of VetChange, an 8-module, cognitive-behavioural intervention. Participants self-selected abstinence or moderation drinking goals, initially at Module 3, and weekly during subsequent modules. Alcohol use and alcohol-related problems were measured using the Alcohol Use Disorders Identification Test (AUDIT), Quick Drink Screen (QDS), and Short Inventory of Problems (SIP-2R). RESULTS: Initial goal choices were 86.9% moderation and 13.1% abstinence. Approximately 20% of participants from each initial choice changed goals during the intervention; last goal choices were 68.6% moderation and 31.4% abstinence. Participants who initially chose moderation reported higher percent heavy drinking days at baseline; participants who initially chose abstinence were more likely to report recent substance abuse treatment and were older. Post-intervention levels of alcohol use and alcohol-related problems were significantly reduced in all goal-choice patterns (i.e., Moderation Only, Abstinence Only, Moderation to Abstinence, and Abstinence to Moderation; all measures p < 0.05 or less). Baseline drinking severity did not differentially relate to outcomes across goal-choice patterns. CONCLUSIONS: Participants in a Web-based alcohol intervention for returning U.S. Veterans demonstrated improvements in drinking regardless of whether they chose an abstinence or moderation drinking goal, and whether the goal was maintained or changed over the course of the intervention.

Temporal stability of DSM-5 posttraumatic stress disorder criteria in a problem-drinking sample.

The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reformulated posttraumatic stress disorder (PTSD) based partially on research showing there were 4 main factors that underlie the symptoms of the disorder. The primary aim of this study was to examine the temporal stability of the DSM-5 factors as measured by the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5; Weathers et al., 2010). Confirmatory factor analyses were conducted to examine the structure of DSM-5 PTSD, and temporal stability over 3 time points was examined to determine if the measure reflects a consistent construct over time. Our sample was 507 combat-exposed veterans of Iraq and Afghanistan who enrolled in an online intervention for problem drinking and combat-related stress (Brief et al., 2013). We administered the PCL-5 at baseline, 8-week postintervention, and 3-month follow-up assessments. The DSM-5 model provided an adequate fit to the data at baseline. Tests of equality of form and equality of factor loadings demonstrated stability of the factor structure over time, indicating temporal stability. This study confirmed the results of previous research supporting the DSM-5 model of PTSD symptoms (Elhai et al., 2012; Miller et al., 2013). This is the 1st study to demonstrate the temporal stability of the PCL-5, indicating its use in longitudinal studies measures the same construct over time.