Identifying effective vaccine champions: Findings from a national survey of primary care professionals.

BACKGROUND: Vaccine champions are common in primary care, but little is known about which champions are effective. METHODS: In 2022, we surveyed 2,144 US primary care professionals (PCPs) who reported working with vaccine champions. Respondents rated the champion with whom they worked most closely on their effectiveness at improving vaccination rates. RESULTS: About half (49 %) of PCPs perceived their closest champion as highly effective. PCPs perceived advanced practice providers and nursing staff as highly effective somewhat more often than physicians (52 % and 58 % vs 43 %, p <.001). Other correlates of perceived effectiveness included being a formally appointed versus informal champion, working extremely versus less closely with PCPs, and using a high (4-5) versus low (0-1) number of implementation strategies to improve vaccination rates (all p <.001). CONCLUSIONS: Results suggest vaccine champions may benefit from having formal roles and opportunities to work closely with colleagues to improve vaccination rates using multiple strategies.

Structural differences contributing to sex-specific associations between FN BMD and whole-bone strength for adult White women and men.

Hip areal BMD (aBMD) is widely used to identify individuals with increased fracture risk. Low aBMD indicates low strength, but this association differs by sex with men showing greater strength for a given aBMD than women. To better understand the structural basis giving rise to this sex-specific discrepancy, cadaveric proximal femurs from White female and male donors were imaged using nano-CT and loaded in a sideways fall configuration to assess strength. FN pseudoDXA images were generated to identify associations among structure, aBMD, and strength that differ by sex. Strength correlated significantly with pseudoDXA aBMD for females (R2 = 0.468, P < .001) and males (R2 = 0.393, P < .001), but the elevations (y-intercepts) of the linear regressions differed between sexes (P < .001). Male proximal femurs were 1045 N stronger than females for a given pseudoDXA aBMD. However, strength correlated with pseudoDXA BMC for females (R2 = 0.433, P < .001) and males (R2 = 0.443, P < .001) but without significant slope (P = .431) or elevation (P = .058) differences. Dividing pseudoDXA BMC by FN-width, total cross-sectional area, or FN-volume led to significantly different associations between strength and the size-adjusted BMC measures for women and men. Three structural differences were identified that differentially affected aBMD and strength for women and men: First, men had more bone mass per unit volume than women; second, different cross-sectional shapes resulted in larger proportions of bone mass orthogonal to the DXA image for men than women; and third, men and women had different proportions of cortical and trabecular bone relative to BMC. Thus, the proximal femurs of women were not smaller versions of men but were constructed in fundamentally different manners. Dividing BMC by a bone size measure was responsible for the sex-specific associations between hip aBMD and strength. Thus, a new approach for adjusting measures of bone mass for bone size and stature is warranted.

Who are vaccine champions and what implementation strategies do they use to improve adolescent HPV vaccination? Findings from a national survey of primary care professionals.

BACKGROUND: Implementation science researchers often cite clinical champions as critical to overcoming organizational resistance and other barriers to the implementation of evidence-based health services, yet relatively little is known about who champions are or how they effect change. To inform future efforts to identify and engage champions to support HPV vaccination, we sought to describe the key characteristics and strategies of vaccine champions working in adolescent primary care. METHODS: In 2022, we conducted a national survey with a web-based panel of 2527 primary care professionals (PCPs) with a role in adolescent HPV vaccination (57% response rate). Our sample consisted of pediatricians (26%), family medicine physicians (22%), advanced practice providers (24%), and nursing staff (28%). Our survey assessed PCPs' experience with vaccine champions, defined as health care professionals "known for helping their colleagues improve vaccination rates." RESULTS: Overall, 85% of PCPs reported currently working with one or more vaccine champions. Among these 2144 PCPs, most identified the champion with whom they worked most closely as being a physician (40%) or nurse (40%). Almost all identified champions worked to improve vaccination rates for vaccines in general (45%) or HPV vaccine specifically (49%). PCPs commonly reported that champion implementation strategies included sharing information (79%), encouragement (62%), and vaccination data (59%) with colleagues, but less than half reported that champions led quality improvement projects (39%). Most PCPs perceived their closest champion as being moderately to extremely effective at improving vaccination rates (91%). PCPs who did versus did not work with champions more often recommended HPV vaccination at the earliest opportunity of ages 9-10 rather than later ages (44% vs. 33%, p < 0.001). CONCLUSIONS: Findings of our national study suggest that vaccine champions are common in adolescent primary care, but only a minority lead quality improvement projects. Interventionists seeking to identify champions to improve HPV vaccination rates can expect to find them among both physicians and nurses, but should be prepared to offer support to more fully engage them in implementing interventions.

Identifying Healthcare Professionals With Lower Human Papillomavirus (HPV) Vaccine Recommendation Quality: A Systematic Review.

PURPOSE: Strengthening healthcare professionals' (HCPs) communication is an evidence-based approach to increasing human papillomavirus (HPV) vaccine uptake among adolescents. To better target future interventions, we sought to synthesize evidence on HCP subgroups who most need to improve their HPV vaccine recommendation quality. METHODS: We searched five databases for quantitative studies published from 2012 to 2022 on HPV vaccine recommendation quality, including recommendation consistency and strength, for United States adolescents. Two coders independently abstracted data from each eligible study, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We summarized variation in recommendation quality by clinical and HCP characteristics. RESULTS: The 28 eligible studies indicated that relatively low proportions of HCPs used higher-quality recommendation practices (median: 61% across 30 measures) and that recommendation quality varied across HCP subgroups. The most consistent findings were that more pediatric HCPs used higher-quality recommendations than family medicine HCPs (8 of 11 studies, 2-60 percentage point difference) and that HPV-related knowledge was associated with higher recommendation quality (four of seven studies). Most studies observed no differences in recommendation quality by clinical role (e.g., provider vs. nurse) or HCP demographics (e.g., gender, age, race/ethnicity). DISCUSSION: Studies suggest a substantial need to improve HCPs' recommendation quality, with opportunities for targeting future interventions.

Using Cost Conversations to Address Financial Toxicity in Pediatric Asthma Care: Findings From a Survey of Caregivers.

INTRODUCTION: Asthma care teams are well-positioned to help caregivers address financial toxicity in pediatric asthma care, although discussing cost can be challenging. We sought to characterize cost conversations in pediatric asthma specialty care. METHOD: We surveyed 45 caregivers of children aged 4-17 with asthma. Eligible caregivers reported costs concerns and had accompanied their child to a multisite asthma specialty practice in North Carolina. RESULTS: About one-third of caregivers reported a cost conversation (36%). Cost conversations were less common among caregivers whose child had public versus private health insurance (16% vs. 56%), who attended a telehealth versus in-person visit (6% vs. 52%), or who did not versus did want a conversation (19% vs. 77%, all p < .05). Common cost conversation topics were medications and equipment like spacers. DISCUSSION: Our findings suggest cost conversations may be relatively uncommon in pediatric asthma care, particularly for publicly insured patients and telehealth visits.

Implementing an Oncology Nurse Practitioner Fellowship: Reflections and Lessons Learned.

As oncology nurse practitioner (NP) fellowships expand across the United States, institutions note improved transitions to specialty practice and better patient outcomes. These fellowships may further serve as a strategy to a.

Efficacy of DigiKnowItNews: Teen, a multimedia educational website for adolescents about pediatric clinical trials: study protocol for a randomized controlled trial.

BACKGROUND: Pediatric research is crucial for the development of new scientific advancements, treatments, and therapies for adolescents. Yet relatively few pediatric clinical trials are conducted due to barriers to successful recruitment and retention, including knowledge and attitudes about clinical trials. Adolescents tend to experience greater autonomy to make decisions and have expressed interest in being part of the decision to participate in clinical trials. Increasing knowledge, positive attitudes, and self-efficacy related to clinical trials could positively impact the decision to participate in a pediatric clinical trial. However, there are currently few interactive, developmentally appropriate, web-based resources available to educate adolescents about clinical trials. DigiKnowItNews: Teen was created as a multimedia educational website to address the relatively low levels of enrollment in pediatric clinical trials and need for information to empower adolescents to make decisions about participating in clinical trials. METHODS: This is a parallel group randomized controlled superiority trial to test the effectiveness of DigiKnowItNews: Teen, for improving factors related to clinical trial participation among adolescent and parents. Eligible parent-adolescent (ages 12 to 17 years) pairs will be randomly assigned to one of two conditions: intervention or wait-list control. All participants will complete pre- and post-test questionnaires and participants assigned to the intervention will receive access to review the DigiKnowItNews: Teen content for 1 week. Wait-list control participants will have the option to review DigiKnowItNews: Teen after study completion. The primary outcomes are knowledge about clinical research, attitudes, and beliefs toward pediatric clinical trials, self-efficacy for making decisions related to clinical trial participation, willingness to participate in a future clinical trial, procedural fears, and parent-adolescent communication quality. Overall feedback and satisfaction related to DigiKnowItNews: Teen will also be collected. DISCUSSION: The trial will evaluate the effectiveness of DigiKnowIt News: Teen, an educational website about pediatric clinical trials for adolescents. If found effective in promoting factors related to future pediatric clinical trial participation, DigiKnowIt News: Teen could be used by adolescents, along with their parents, as they make the decision to participate in a clinical trial. Clinical trial researchers can also use DigiKnowIt News: Teen to aid their participant recruitment efforts. TRIAL REGISTRATION: ClinicalTrials.gov NCT05714943. Registered on 02/03/2023.

A randomized, sham-controlled trial of a novel near-infrared phototherapy device on sleep and daytime function.

STUDY OBJECTIVES: Near-infrared light exhibits several therapeutic properties, but little is known about the benefits to sleep and daytime function. The purpose of this study was to investigate the effects of red and near-infrared exposure before bed on sleep and next-day function. METHODS: Thirty adults (30-60 y) with a self-reported sleep complaint but without a sleep disorder participated in a randomized, sham-controlled study for a duration of 5 weeks. After a 2-week baseline period, participants wore either a cervical red light/near-infrared-emitting collar (combined: 660 nm, 740 nm, 810 nm, and 870 nm) or sham device every other night before bed for 3 weeks. Sleep was measured using actigraphy and sleep diaries. Mood and performance were assessed using weekly self-reported surveys and debrief interviews. RESULTS: Objective sleep parameters, as measured by actigraphy, did not differ between the active or sham groups, but improved self-reported sleep, as well as perceived improvements in relaxation and mood, were observed among active but not sham users. Both active and sham users improved in Insomnia Severity Index score by the end of the trial. CONCLUSIONS: Red and near-infrared exposure to the head and neck before bed may offer potential therapeutic benefits to sleep and daytime function, but further work needs to be done to determine optimal dose parameters, wavelengths, and milliwatt power level. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Phase II Study-Trial of a Phototherapy Light Device to Improve Sleep Health (PHOTONS); URL: https://clinicaltrials.gov/ct2/show/NCT05116358; Identifier: NCT05116358. CITATION: Kennedy KER, Wills CCA, Holt C, Grandner MA. A randomized, sham-controlled trial of a novel near-infrared phototherapy device on sleep and daytime function. J Clin Sleep Med. 2023;19(9):1669-1675.

Associations Among Hip Structure, Bone Mineral Density, and Strength Vary With External Bone Size in White Women.

Bone mineral density (BMD) is heavily relied upon to reflect structural changes affecting hip strength and fracture risk. Strong correlations between BMD and strength are needed to provide confidence that structural changes are reflected in BMD and, in turn, strength. This study investigated how variation in bone structure gives rise to variation in BMD and strength and tested whether these associations differ with external bone size. Cadaveric proximal femurs (n = 30, White women, 36-89+ years) were imaged using nanocomputed tomography (nano-CT) and loaded in a sideways fall configuration to assess bone strength and brittleness. Bone voxels within the nano-CT images were projected onto a plane to create pseudo dual-energy X-ray absorptiometry (pseudo-DXA) images consistent with a clinical DXA scan. A validation study using 19 samples confirmed pseudo-DXA measures correlated significantly with those measured from a commercially available DXA system, including bone mineral content (BMC) (R 2  = 0.95), area (R 2  = 0.58), and BMD (R 2  = 0.92). BMD-strength associations were conducted using multivariate linear regression analyses with the samples divided into narrow and wide groups by pseudo-DXA area. Nearly 80% of the variation in strength was explained by age, body weight, and pseudo-DXA BMD for the narrow subgroup. Including additional structural or density distribution information in regression models only modestly improved the correlations. In contrast, age, body weight, and pseudo-DXA BMD explained only half of the variation in strength for the wide subgroup. Including bone density distribution or structural details did not improve the correlations, but including post-yield deflection (PYD), a measure of bone material brittleness, did increase the coefficient of determination to more than 70% for the wide subgroup. This outcome suggested material level effects play an important role in the strength of wide femoral necks. Thus, the associations among structure, BMD, and strength differed with external bone size, providing evidence that structure-function relationships may be improved by judiciously sorting study cohorts into subgroups. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Leveraging Telemedicine to Reduce the Financial Burden of Asthma Care.

One of the most compelling arguments for telemedicine is its potential to increase health care access by making care more affordable for patients and families, including those affected by asthma. This goal is critically important in the United States, where the high cost of asthma care is associated with nonadherence to preventive care regimens and suboptimal health outcomes. In this clinical commentary review, we draw from the literature and our own research to identify opportunities for and challenges to leveraging telemedicine to reduce the financial burden of asthma care. Our interviews with 42 families affected by asthma during the COVID-19 pandemic suggest that under favorable circumstances, telemedicine can meaningfully reduce costs, including those related to transportation and missed work, while offering high-quality care. However, families also identified ways in which telemedicine can increase costs. For example, some reported reduced access to support services and material resources such as medication samples, which they relied on to manage costs. In this way, our findings underscore the need for careful care coordination and communication in telemedicine. We conclude by discussing the 4Rs, a structured communication approach designed to support cost conversations, increase care coordination, and help families reduce asthma care cost burden.

Nightmare content during the COVID-19 pandemic: Influence of COVID-related stress and sleep disruption in the United States.

Nightmares are often associated with psychiatric disorders and acute stress. This study explores how the COVID-19 pandemic may have influenced the content of nightmares. A sample of N = 419 US adults completed online surveys about sleep and COVID-19 experiences. Participants were asked about the degree to which they agreed with statements linking greater general stress, worse overall sleep and more middle-of-the-night insomnia with the COVID-19 pandemic. They were also asked if, during the pandemic, they experienced nightmares related to various themes. Logistic regression analyses examined each nightmare content as outcome and increased stress, worse sleep and more middle-of-the-night insomnia as predictors, adjusted for age, sex and race/ethnicity. Those who reported greater general COVID-related stress were more likely to have nightmares about confinement, failure, helplessness, anxiety, war, separation, totalitarianism, sickness, death, COVID and an apocalypse. Those who reported worsened sleep were more likely to have nightmares about confinement, oppression, failure, helplessness, disaster, anxiety, evil forces, war, domestic abuse, separation, totalitarianism, sickness, death, COVID and an apocalypse. Those who reported worsened middle-of-the-night insomnia were more likely to have nightmares about confinement, oppression, failure, helplessness, disaster, anxiety, war, domestic abuse, separation, totalitarianism, sickness, death, COVID and an apocalypse. These results suggest that increased pandemic-related stress may induce negatively-toned dreams of specific themes. Future investigation might determine whether (and when) this symptom indicates an emotion regulation mechanism at play, or the failure of such a mechanism.

Menstrual regularity and bleeding is associated with sleep duration, sleep quality and fatigue in a community sample.

Female menstrual health and its relationship with sleep is an understudied subject. The aim of this investigation was to determine the association between the two in a community sample. Data were obtained from n = 579 menstruating females who participated in the Sleep and Health Activity, Diet, Environment, and Socialization (SHADES) study, a community-based sample of adults aged 22-60 years. Participants were asked, "How regular is your period?", with response choices of "very regular", "mostly regular", "fairly regular" and "not regular". They were also asked, "How much bleeding do you usually experience during your period?" Response choices were: "very heavy", "heavy", "medium", "light" or "very light". These were evaluated as ordinal outcomes. Sleep-related predictors included sleep duration (in hr; ≤ 6 [short], 7-9 [normal] and ≥ 9 [long]), Insomnia Severity Index score, Pittsburgh Sleep Quality Index score, Epworth Sleepiness Scale score and Fatigue Severity Scale score. Covariates included age, education, income, race/ethnicity and body mass index. Short sleep duration was associated with heavier bleeding (odds ratio = 1.46, p = 0.026) and greater cycle irregularity (odds ratio = 1.44, p = 0.031) as compared with normal sleep. Higher Pittsburgh Sleep Quality Index score was associated with greater cycle irregularity (odds ratio = 1.05, p = 0.022). Higher Fatigue Severity Scale score was associated with heavier bleeding (odds ratio = 1.02, p = 0.003) and greater cycle irregularity (odds ratio = 1.02, p = 0.008). Long sleep, Insomnia Severity Index and Epworth Sleepiness Scale were not associated with either outcome. These results demonstrate an association between short sleep duration, poor sleep quality, fatigue, stress and depression with heavier bleeding and menstrual cycle irregularity, highlighting the need for further studies to improve treatment options.

Sleep, Dreams, and Nightmares During the COVID-19 Pandemic.

The COVID-19 pandemic has affected the sleep and dreams of many individuals. Some have experienced improvements, while others have had more complaints. The changes to daily life such as working from home and spending more time indoors in confinement may have disturbed the circadian rhythms of some individuals. There were many reports of a shift towards a later bedtime during the pandemic, with several studies showing that in general, females experienced worse sleep than males, including more nighttime awakenings and nightmares. Increased dream and nightmare frequency during the pandemic has been shown in multiple studies. It has been postulated that because dreams are often guided by the dominant emotional state, that dreams and nightmares related to pandemic themes are a result of specific stressors related to COVID-19. Those experiencing unwanted sleep disturbances and nightmares could stand to benefit from mindfulness and relaxation practices that can ease stress and anxiety before bedtime. Striving to maintain a regular sleep schedule and enhance exposure to daylight-particularly during the first half of the day-may also be helpful.

A Randomized, Double-Blind, Placebo-Controlled Trial of a Polyphenol Botanical Blend on Sleep and Daytime Functioning.

Despite the high prevalence of subclinical sleep disturbances, existing treatments are either potent prescription medications or over-the-counter supplements with minimal scientific support and numerous side effects. However, preliminary evidence shows that polyphenols such as rosmarinic acid and epigallocatechin gallate can support healthy sleep without significant side effects. Therefore, the present study examined whether a polyphenol botanical blend (PBB) could improve sleep and/or daytime functioning in individuals with subclinical sleep disturbances. A total of 89 individuals completed a double-blind, randomized trial of daily treatment with PBB (n = 43) or placebo (n = 46) 30 min before bed for 30 days. Participants were monitored for changes in sleep (by sleep diary and an activity tracker), mood, and neurocognitive functioning. After 30 days, PBB improved diary sleep quality (p = 0.008) and reduced insomnia severity (p = 0.044) when compared to placebo. No other changes in sleep outcomes were observed. Additionally, PBB did not impair neurocognitive functioning, and some improvement was noted in vigilant attention, working memory, and risk assessment. Among individuals with subclinical sleep disturbances, PBB improved sleep quality, insomnia severity, and neurocognitive functioning over placebo. These findings indicate that polyphenol compounds may be useful for improving certain aspects of sleep without compromising neurocognitive functioning.

Vascular plant extinction in the continental United States and Canada.

Extinction rates are expected to increase during the Anthropocene. Current extinction rates of plants and many animals remain unknown. We quantified extinctions among the vascular flora of the continental United States and Canada since European settlement. We compiled data on apparently extinct species by querying plant conservation databases, searching the literature, and vetting the resulting list with botanical experts. Because taxonomic opinion varies widely, we developed an index of taxonomic uncertainty (ITU). The ITU ranges from A to F, with A indicating unanimous taxonomic recognition and F indicating taxonomic recognition by only a single author. The ITU allowed us to rigorously evaluate extinction rates. Our data suggest that 51 species and 14 infraspecific taxa, representing 33 families and 49 genera of vascular plants, have become extinct in our study area since European settlement. Seven of these taxa exist in cultivation but are extinct in the wild. Most extinctions occurred in the west, but this outcome may reflect the timing of botanical exploration relative to settlement. Sixty-four percent of extinct plants were single-site endemics, and many occurred outside recognized biodiversity hotspots. Given the paucity of plant surveys in many areas, particularly prior to European settlement, the actual extinction rate of vascular plants is undoubtedly much higher than indicated here.

Extinción de las Plantas Vasculares en Canadá y los Estados Unidos Continentales Resumen Se espera que las tasas de extinción aumenten durante el Antropoceno. Todavía desconocemos las tasas de extinción actuales de las plantas y muchos animales. Cuantificamos las tasas de extinción de la flora vascular de los Estados Unidos Continentales y Canadá a partir del asentamiento de los europeos. Recopilamos datos sobre especies aparentemente extintas mediante la consulta de bases de datos sobre conservación, búsquedas en la literatura y el escrutinio de la lista resultante con botánicos expertos. Ya que la opinión taxonómica varía ampliamente, desarrollamos un índice de incertidumbre taxonómica (ITU). La ITU abarca desde la A hasta la F, en donde la A indica un reconocimiento taxonómico unánime y la F indica el reconocimiento taxonómico por un sólo autor. La ITU nos permitió evaluar rigurosamente las tasas de extinción. Nuestros datos sugieren que 51 especies y 14 taxones infraespecíficos, que en conjunto representan a 33 familias y a 49 géneros de plantas vasculares, se han extinguido en nuestra área de estudio desde el asentamiento de los europeos. Siete de estos taxones existen en cultivos, pero se encuentran extintos en vida libre. La mayoría de las extinciones ocurrieron en la parte oeste del área de estudio, aunque este resultado puede reflejar el momento de la exploración botánica en relación con el asentamiento europeo. El 64% de las plantas extintas eran endémicas de un sitio único y muchas tuvieron presencia fuera de los puntos calientes de biodiversidad. Dada la escasez de los censos botánicos en muchas áreas, particularmente previo al asentamiento europeo, la tasa actual de extinción de las plantas vasculares es sin duda mucho más alta de lo que se indica en este estudio.

Forward collision warning system impact.

OBJECTIVE: The objective of this research is to use historical crash data to evaluate the potential benefits of both high- and low-speed automatic emergency braking (AEB) with forward collision warning (FCW) systems. METHODS: Crash data from the NHTSA's NASS-General Estimates System (GES) and Fatality Analysis Reporting System (FARS) databases were categorized to classify crashes by the speed environment, as well as to identify cases where FCW systems would be applicable. RESULTS: Though only about 19% of reported crashes occur in environments with speeds greater than 45 mph, approximately 32% of all serious or fatal crashes occur in environments with speeds greater than 45 mph. The percentage of crashes where FCW systems would be relevant has remained remarkably constant, varying between about 21 and 26% from 2002 to 2015. In 2-vehicle fatal crashes where one rear-ends the other, the fatality rates are actually higher in the struck vehicle (33%) than the striking vehicle (26%). The disparity is even greater when considering size-class differences, such as when a light truck rear-ends a passenger car (15 vs. 42% fatality rates, respectively). CONCLUSIONS: NHTSA and the Insurance Institute for Highway Safety (IIHS) proposed the Automatic Emergency Braking Initiative in 2015, which is intended to make AEB (also called crash-imminent braking) with FCW systems standard on nearly all new cars by September 2022. Twenty automakers representing 99% of the U.S. auto market voluntarily committed to the initiative. Though the commitment to safety is laudable, the AEB component of the agreement only covers low-speed AEB systems, with the test requirements set to 24 mph or optionally as low as 12 mph. The test requirements for the FCW component of the agreement include 2 tests that begin at 45 mph. Only 21% of relevant serious injury or fatal accidents occur in environments at speeds under 24 mph, whereas about 22% of serious or fatal crashes occur in environments with speeds greater than 45 mph. This means that the AEB with FCW systems as agreed upon will cover only 21% of serious or fatal crashes and will not cover 22% of serious or fatal crashes. Because these systems are protective not only for the occupants of the vehicle where they are installed but also other vehicles on the roads, the data indicate that these systems should be a standard feature on all cars for high-speed as well as low-speed environments for the greatest social benefit.

Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study.

PURPOSE: To assess the efficacy and safety of lifitegrast ophthalmic solution 5.0% compared with placebo in subjects with dry eye disease. DESIGN: Prospective, randomized, double-masked, placebo-controlled, parallel arm, multicenter clinical trial. PARTICIPANTS: A total of 588 adult subjects with dry eye disease. METHODS: Eligible subjects were randomized 1:1 to receive topically administered lifitegrast (5.0%) or placebo (vehicle) twice daily for 84 days after a 14-day open-label placebo run-in period. After enrollment (day 0), subjects were evaluated at days 14, 42, and 84. Key objective (fluorescein and lissamine staining scores [Ora scales]) and subjective (Ocular Surface Disease Index [OSDI], 7-item visual analog scale, and ocular discomfort score [Ora scale]) measures were assessed at all visits. MAIN OUTCOME MEASURES: The primary objective efficacy measure (sign) was mean change from baseline inferior corneal staining score (ICSS) at day 84. The co-primary subjective efficacy measure (symptom) was the mean change from baseline in the visual-related function subscale score of the Ocular Surface Disease Index (VR-OSDI). Supportive measures included corneal fluorescein scores (superior, central, total region) and conjunctival lissamine scores (nasal, temporal, total region) and symptom scores at day 84. RESULTS: The study met the primary objective efficacy ICSS end point in demonstrating superiority of lifitegrast compared with placebo (P = 0.0007). Lifitegrast significantly reduced corneal fluorescein staining (superior, P = 0.0392; total cornea, P = 0.0148) and conjunctival lissamine staining (nasal, P = 0.0039; total conjunctiva, P = 0.0086) at day 84 versus placebo. Significant (P < 0.05) improvements in nasal and total lissamine scores were observed at day 14 and maintained through day 84. The study did not meet the co-primary subjective VR-OSDI measure (P = 0.7894). However, significant improvements were observed at day 84 in ocular discomfort (P = 0.0273) and eye dryness (P = 0.0291), the most common and severe symptoms reported at baseline in both groups. There were no unanticipated or serious ocular adverse events (AEs). The most frequent reported ocular AEs were transient intermittent instillation site symptoms (irritation, discomfort) primarily on the initial lifitegrast dose at day 0. CONCLUSIONS: Lifitegrast ophthalmic solution 5.0% significantly reduced corneal fluorescein and conjunctival lissamine staining and improved symptoms of ocular discomfort and eye dryness compared with placebo when administered twice daily over 84 days.

Synthesis of C2 -Symmetric Dimeric Re(I) Peptide Complexes.

The reactions of [Re(CO)3(H2O)3]Br or Re(CO)5Cl with two peptides, glycylglycine or glycylalanine, were investigated. Each reaction produced a unique, well-defined product. Structural elucidation showed the formation of chiral compounds with the formula [Re(CO)3(Gly-Xxx-O)]2, Xxx = Gly 1, Ala 2. Each dimer displays C2 -symmetry and a nearly rectangular shape. The ligands are bound via the amine and amide carbonyl at a rhenium center and via the pendant carboxylate to the adjacent rhenium center. Both products are fully characterized, via X-ray structure elucidation.