Indirect comparisons of relative efficacy estimates of zuranolone and selective serotonin reuptake inhibitors for postpartum depression.

AIMS: Estimate relative efficacy of zuranolone, a novel oral, Food and Drug Administration-approved treatment for postpartum depression (PPD) in adults vs. selective serotonin reuptake inhibitors (SSRIs) and combination therapies used for PPD in the United States. MATERIALS AND METHODS: Randomized controlled trials (RCTs) for zuranolone and SSRIs, identified from systematic review, were used to construct evidence networks, linking via common comparator arms. Due to heterogeneity in placebo responses, matching-adjusted indirect comparison (MAIC) was applied, statistically weighting the zuranolone treatment arm of Phase 3 SKYLARK Study (NCT04442503) to the placebo arm of RCTs investigating SSRIs for PPD. MAIC outputs were applied in Bucher indirect treatment comparisons (ITCs) and network meta-analysis (NMA), using Edinburgh Postnatal Depression Scale (EPDS) and 17-item Hamilton Rating Scale for Depression (HAMD-17) change from baseline (CFB) on Days 3, 15, 28 (Month 1), 45, and last observation (Day 45, Week 12/18). RESULTS: Larger EPDS CFB was observed among zuranolone-treated vs. SSRI-treated patients from Day 15 onward. Zuranolone-treated (vs. SSRI-treated) patients exhibited 4.22-point larger reduction in EPDS by Day 15 (95% confidence interval: -6.16, -2.28) and 7.43-point larger reduction at Day 45 (-9.84, -5.02) with Bucher ITC. NMA showed EPDS reduction for zuranolone was 4.52 (-6.40, -2.65) points larger than SSRIs by Day 15 and 7.16 (-9.47, -4.85) larger at Day 45. Lack of overlap between study populations substantially reduced effective sample size post-matching, making HAMD-17 CFB analysis infeasible. LIMITATIONS: Limited population overlap between SKYLARK Study and RCTs reduced feasibility of undertaking HAMD-17 CFB ITCs and may introduce uncertainty to EPDS CFB ITC results. CONCLUSIONS: Analysis showed zuranolone-treated patients with PPD experienced greater symptom improvement than SSRI-treated patients from Day 15 onward, with largest mean difference at Day 45. Adjusting for differences between placebo arms, zuranolone may be associated with greater PPD symptom improvement (measured by EPDS) vs. SSRIs.

Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial.

Vorasidenib and ivosidenib inhibit mutant forms of isocitrate dehydrogenase (mIDH) and have shown preliminary clinical activity against mIDH glioma. We evaluated both agents in a perioperative phase 1 trial to explore the mechanism of action in recurrent low-grade glioma (IGG) and select a molecule for phase 3 testing. Primary end-point was concentration of D-2-hydroxyglutarate (2-HG), the metabolic product of mIDH enzymes, measured in tumor tissue from 49 patients with mIDH1-R132H nonenhancing gliomas following randomized treatment with vorasidenib (50 mg or 10 mg once daily, q.d.), ivosidenib (500 mg q.d. or 250 mg twice daily) or no treatment before surgery. Tumor 2-HG concentrations were reduced by 92.6% (95% credible interval (CrI), 76.1-97.6) and 91.1% (95% CrI, 72.0-97.0) in patients treated with vorasidenib 50 mg q.d. and ivosidenib 500 mg q.d., respectively. Both agents were well tolerated and follow-up is ongoing. In exploratory analyses, 2-HG reduction was associated with increased DNA 5-hydroxymethylcytosine, reversal of 'proneural' and 'stemness' gene expression signatures, decreased tumor cell proliferation and immune cell activation. Vorasidenib, which showed brain penetrance and more consistent 2-HG suppression than ivosidenib, was advanced to phase 3 testing in patients with mIDH LGGs. Funded by Agios Pharmaceuticals, Inc. and Servier Pharmaceuticals LLC; ClinicalTrials.gov number NCT03343197.

Direct-to-consumer orthodontics: Exploring laypeople's perception of orthodontic treatment complexity.

BACKGROUND: The authors aimed to explore the treatment preferences of laypeople regarding direct-to-consumer (DTC) orthodontics and to identify whether case complexity, as perceived by laypeople, is one of the factors influencing interest in DTC orthodontics. METHODS: An online cross-sectional survey was conducted. Data analysis was performed using logistic regression models. RESULTS: A total of 1,362 surveys were completed. A significant inverse association was identified between the complexity of an orthodontic case, as measured using the American Board of Orthodontics' discrepancy index (DI) score, and the likelihood of choosing DTC treatment over an orthodontist. Participants were 3.53 times more likely to choose DTC treatment for a mild case (DI score, 0-10) compared with a complex case (DI score, > 20), although the likelihood of choosing DTC treatment for a moderate case (DI score, 11-20) was only 1.79 times higher than for a complex case. CONCLUSIONS: When laypeople were asked to consider each case as if it were their own dentition, there was a significant inverse association between the complexity of an orthodontic case, as measured using the DI score, and the likelihood of choosing DTC treatment over an orthodontist. Laypeople were seemingly more likely to choose DTC orthodontics for dentitions that did not appear crowded and were well aligned within the arches. Laypeople seemed to have an understanding that there are some limitations to DTC orthodontics. PRACTICAL IMPLICATIONS: Orthodontists should better understand the factors influencing consumers' decisions to select DTC orthodontics and dental organizations should focus their educational campaigns on these factors.

Saturdays Orthodontic Appointments, Demand, and Patients' Commitment.

AIM: The purpose of this study was to determine the demand for orthodontic appointments on weekends and the level of commitment the patients have for those appointments. MATERIALS AND METHODS: A survey of 17 questions was created and given to 199 adult patients. The first six questions addressed demographic information, followed by three questions addressing whether coming to their orthodontic appointments required taking time off of work. The remaining questions asked if they would prefer to attend orthodontic appointments on Saturday if they would take advantage of a Saturday appointment, and what their preferred time and level of commitment would be for this appointment. The data were analyzed using the logistic-regression Chi-square test. RESULTS: About 77.4% of the participants indicated that they would take advantage of appointments on Saturdays if available. The most preferred time for Saturday appointments was 7:00 am-10:00 am, followed by 10:00 am-12:00 pm. About 60.6% of the participants reported that they would be willing to sign up for AutoPay in order to be seen on Saturday. Among those who would take advantage of weekend appointments, 82.6% reported that they would likely never miss or reschedule a Saturday appointment, and 75.3% would choose an orthodontist who is open on Saturday over another orthodontist who is not. Among participants who work more than 40 hours per week, 86.1% (106) wanted to take advantage of Saturday appointments. Participants with a high household income are less inclined to take advantage of Saturday appointments compared with those with a low household income. Participants who need to take time off of work are more inclined to take advantage of Saturday appointments [93% (106) favorable vs 7% (8) unfavorable]. Participants who need to take their child out of school early for their orthodontic appointments during the week are more inclined to take advantage of Saturday appointments [87% (97) favorable vs 13% (15) unfavorable] than those who do not need to. CONCLUSION: There is a demand for Saturday orthodontic appointments with a very high commitment level among the majority of those patients. The Saturday demographic tends to be participants with a low household income who work 40 or more hours per week. CLINICAL SIGNIFICANCE: Orthodontic offices may consider working at least one Saturday per month to satisfy patient needs. They can use this survey to explore their own market for Saturday clinical practice.

Correlation between adolescent orthodontic quality of life and ABO Discrepancy Index in an orthodontic treatment-seeking population: A cross-sectional study.

OBJECTIVE: To evaluate the association between adolescents' orthodontic quality of life before initiating orthodontic treatment and their objective case complexity as measured by the American Board of Orthodontics' Discrepancy Index (DI). DESIGN AND SETTING: A single-centre, cross-sectional survey study. METHODS: The Orthodontic Quality of Life Assessment Survey (OQoLAS) was administered to 240 adolescents (aged 11-14 years) during their record-gathering appointment. After completion of the survey, a DI score was calculated for each patient based on pretreatment measurements. Pearson correlation coefficients, r, were used to assess the association of DI scores with OQoLAS total and subdomain scores. A multiple linear regression of OQoLAS total scores adjusting for age, gender and DI scores was conducted. RESULTS: The study did not find a strong correlation between OQoLAS and DI scores (r = 0.10; P = 0.6497). On average, the OQoLAS scores (functional, emotional and social subdomains of OQoLAS) were slightly higher among girls than among boys but there was no statistical difference for total OQoLAS score between boys and girls (42.4 vs. 45.4, P = 0.2005). However, there was a significant difference in oral health perception rating between boys and girls, with girls being more likely to rate their oral health positively (adjusted P = 0.0226). The total DI scores of boys with respect to girls were not statistically different (P = 0.4256). The components of the DI that showed highest score were for cephalometric measures, followed by overjet; and the lowest scores were for lateral open bite and buccal posterior crossbite. The measure of association analysis did not show any strong correlation between the OQoLAS (total score and subdomain scores), and DI score or any of its components. CONCLUSION: Malocclusion severity was not found to be correlated with orthodontic quality of life in adolescents aged 11-14 years seeking orthodontic treatment.

Direct to consumer orthodontics: Exploring patient demographic trends and preferences.

INTRODUCTION: This study aimed to evaluate market trends on the demographics most likely to select direct to consumer orthodontics and the reasoning behind their decisions. METHODS: An internet-based cross-sectional survey was conducted. Data analysis was carried out using logistic regression models. RESULTS: Total of 1573 surveys were completed. While 32.2% of those surveyed selected direct to consumer orthodontics over conventional orthodontics, 10.8% would select direct to consumer orthodontics for their children. Among parents who would seek direct to consumer orthodontics, only 27.8% would consider the same treatment for their children. The odds of seeking direct to consumer orthodontic treatment for divorced participants was 2.52 times higher than that for single participants, for participants with 4 children or more was 2 times higher than that for participant with no children, and in age group 46-59 years was 2.23 times higher than that for age group 18-26 years. Seventy three percent of consumers who selected direct to consumer orthodontics selected cost as an influencing factor. Convenience was also a major determining factor at 69.6%. CONCLUSIONS: Cost, convenience, and perceived simplicity all appear to factor into a consumer's consideration of direct to consumer orthodontics. As annual household income, age, and education increases consumers are more likely to consider direct to consumer orthodontic treatment.

Efficacy in myopia control.

There is rapidly expanding interest in interventions to slow myopia progression in children and teenagers, with the intent of reducing risk of myopia-associated complications later in life. Despite many publications dedicated to the topic, little attention has been devoted to understanding 'efficacy' in myopia control and its application. Treatment effect has been expressed in multiple ways, making comparison between therapies and prognosis for an individual patient difficult. Available efficacy data are generally limited to two to three years making long-term treatment effect uncertain. From an evidence-based perspective, efficacy projection should be conservative and not extend beyond that which has been empirically established. Using this principle, review of the literature, data from our own clinical studies, assessment of demonstrated myopia control treatments and allowance for the limitations and context of available data, we arrive at the following important interpretations: (i) axial elongation is the preferred endpoint for assessing myopic progression; (ii) there is insufficient evidence to suggest that faster progressors, or younger myopes, derive greater benefit from treatment; (iii) the initial rate of reduction of axial elongation by myopia control treatments is not sustained; (iv) consequently, using percentage reduction in progression as an index to describe treatment effect can be very misleading and (v) cumulative absolute reduction in axial elongation (CARE) emerges as a preferred efficacy metric; (vi) maximum CARE that has been measured for existing myopia control treatments is 0.44 mm (which equates to about 1 D); (vii) there is no apparent superior method of treatment, although commonly prescribed therapies such as 0.01% atropine and progressive addition spectacles lenses have not consistently provided clinically important effects; (viii) while different treatments have shown divergent efficacy in the first year, they have shown only small differences after this; (ix) rebound should be assumed until proven otherwise; (x) an illusion of inflated efficacy is created by measurement error in refraction, sample bias in only treating 'measured' fast progressors and regression to the mean; (xi) decision to treat should be based on age of onset (or refraction at a given age), not past progression; (xii) the decreased risk of complications later in life provided by even modest reductions in progression suggest treatment is advised for all young myopes and, because of limitations of available interventions, should be aggressive.

The effects of light scatter when using a photochromic vs. non-photochromic contact lens / Efectos de la dispersión luminosas al utilizar lentes de contacto fotocromáticas vs. no fotocromáticas

PURPOSE: To assess the visual effects of wearing both an activated and an inactivated photochromic contact lens, with a direct comparison to a non-photochromic contact lens worn in the fellow eye. This study focused on the visual effects of scatter quantified as the minimum distance between two points of light, and the diameter of the halo and starbursts that surround a bright white point source. METHODS: 60 subjects (aged 18-65 years) were measured in a contralateral design where lens type was randomly assigned, one type to each eye. During activated testing, all visual measures of both study lenses were made while each eye was illuminated by a violet (Lambdamax = 365, half bandwidth 20 nm) activator, which caused steady-state activation of the photochromic lens during the period of testing. Two-point thresholds were determined by measuring the minimum distance between two points of broadband xenon light. Glare geometry was measured using an aperture (∼ 4 mm) that created a bright point source of light 45 inches from the plane of the eye. Between the point source and subject, a centering precision caliper was used to measure lateral spread of halos (diffusion around the source) and visual spokes. The head was stabilized using an adjustable head-rest assembly and the eye was aligned and monitored with a bore camera. RESULTS: Compared to the non-photochromic lens, and based on the stimulus conditions used in these measurements, the activated and inactivated photochromic lens reduced the light spread using the two-point threshold technique by 32% and 19% respectively; the diameter of the halos were reduced by 44% and 16% respectively; and the spokes were narrowed by 39% and 20% respectively. Based on 95% confidence interval testing, these effects were all statistically significant (p < 0.05). CONCLUSIONS: These results are consistent with previous data showing that soft contact lenses with a photochromic additive can improve many aspects of visual function, consistent with their level or activation. Our past data focused on visual function under bright light conditions (e.g., glare disability, discomfort, photostress recovery and chromatic contrast) with an activated photochromic. In this study, we found differences even in the inactivated state, using less intense stimuli (10cd/m2 at the source). This suggests that the photochromic lens improves the effects of light scatter even at lower luminance

OBJETIVO: Evaluar los efectos visuales del uso de lentes de contacto con activación e inactivación fotocromática, mediante comparación directa con el uso de lentes de contacto no fotocromáticas en el ojo contralateral. Este estudio se centró en los efectos visuales de la dispersión, cuantificada mediante la distancia mínima entre dos puntos luminosos, y el diámetro del halo y los destellos que rodean a una fuente fija blanca brillante. MÉTODOS: Se realizaron mediciones a 60 sujetos (de edades comprendidas entre 18 y 65 años) en un diseño contralateral en el que se asignó aleatoriamente un tipo a cada ojo. Durante la prueba con activación, se realizaron todas las medidas visuales de ambas lentes en estudio, mientras se iluminaba cada ojo con un activador violeta (lambdamáx.=365, ancho de banda medio 20 nm), que causó una activación del estado de equilibrio de las lentes fotocromáticas durante el periodo de prueba. Se determinaron los umbrales de dos puntos, midiendo la distancia mínima entre dos puntos de luz de xenón de banda ancha. Se midió la geometría del reflejo utilizando una apertura (∼ 4 mm) que creó una fuente fija brillante de luz a 45 pulgadas del plano del ojo. Entre la fuente fija y el sujeto se utilizó un calibrador de precisión de centrado para medir la expansión lateral de los halos (difusión alrededor de la fuente) y los destellos. La cabeza se estabilizó utilizando un reposacabezas, alineándose y supervisándose el ojo con una cámara. RESULTADOS: Realizando una comparación con las lentes no fotocromáticas, y sobre la base de las condiciones de estímulo utilizadas en estas medidas, las lentes con activación y desactivación fotocromática redujeron la expansión de la luz utilizando la técnica del umbral de dos puntos en un 32% y un 19% respectivamente; el diámetro de los halos se redujo en un 44% y 16% respectivamente; y los brillos se estrecharon en un 39% y 20% respectivamente. Basándonos en la prueba del intervalo de confianza del 95%, todos estos efectos fueron estadísticamente significativos (p < 0,05). CONCLUSIONES: Estos resultados son consistentes con los datos previos, que reflejan que las lentes de contacto fotocromáticas pueden mejorar muchos aspectos de la función visual, en consistencia con su nivel de activación. Nuestros datos anteriores se centraron en la función visual en condiciones de luz brillante (ej.: incapacidad por deslumbramiento, incomodidad, recuperación de foto-estrés y contraste cromático) con activación de adición fotocromática. En este estudio, encontramos diferencias incluso en el estado de inactivación, utilizando estímulos menos intensos (10 cd/m2 en la fuente), lo cual sugiere que las lentes fotocromáticas mejoran los efectos de la dispersión luminosa incluso con una luminancia menor

The effects of light scatter when using a photochromic vs. non-photochromic contact lens.

PURPOSE: To assess the visual effects of wearing both an activated and an inactivated photochromic contact lens, with a direct comparison to a non-photochromic contact lens worn in the fellow eye. This study focused on the visual effects of scatter quantified as the minimum distance between two points of light, and the diameter of the halo and starbursts that surround a bright white point source. METHODS: 60 subjects (aged 18-65 years) were measured in a contralateral design where lens type was randomly assigned, one type to each eye. During activated testing, all visual measures of both study lenses were made while each eye was illuminated by a violet (λmax=365, half bandwidth 20nm) activator, which caused steady-state activation of the photochromic lens during the period of testing. Two-point thresholds were determined by measuring the minimum distance between two points of broadband xenon light. Glare geometry was measured using an aperture (∼4mm) that created a bright point source of light 45 inches from the plane of the eye. Between the point source and subject, a centering precision caliper was used to measure lateral spread of halos (diffusion around the source) and visual spokes. The head was stabilized using an adjustable head-rest assembly and the eye was aligned and monitored with a bore camera. RESULTS: Compared to the non-photochromic lens, and based on the stimulus conditions used in these measurements, the activated and inactivated photochromic lens reduced the light spread using the two-point threshold technique by 32% and 19% respectively; the diameter of the halos were reduced by 44% and 16% respectively; and the spokes were narrowed by 39% and 20% respectively. Based on 95% confidence interval testing, these effects were all statistically significant (p<0.05). CONCLUSIONS: These results are consistent with previous data showing that soft contact lenses with a photochromic additive can improve many aspects of visual function, consistent with their level or activation. Our past data focused on visual function under bright light conditions (e.g., glare disability, discomfort, photostress recovery and chromatic contrast) with an activated photochromic. In this study, we found differences even in the inactivated state, using less intense stimuli (10cd/m2 at the source). This suggests that the photochromic lens improves the effects of light scatter even at lower luminance.

Randomized Crossover Trial Evaluating the Impact of Senofilcon A Photochromic Lens on Driving Performance.

SIGNIFICANCE: The first contact lens to incorporate a photochromic additive was cleared by the U.S. Food and Drug Administration last year. Because any ophthalmic lens that absorbs visible wavelengths will reduce retinal illuminance, it is important to understand the impact of this new photochromic contact lens on vision and both daytime and nighttime driving performance. PURPOSE: The purpose of this study was to evaluate the effect of senofilcon A photochromic contact lens wear on vision and driving performance under real-world conditions by comparison with a nonphotochromic contact lens and plano photochromic spectacles. METHODS: In this randomized four-visit bilateral crossover study, 24 licensed regular drivers and established wearers of soft contact lenses were enrolled. Subjects wore in random order each of three study lens types: the investigational photochromic soft contact lens (test), a nonphotochromic soft contact lens (control 1), and plano photochromic spectacle lenses (control 2). Driver performance was assessed on a closed-circuit driving track under challenging controlled conditions. The primary endpoint was overall driving performance score calculated as a composite Z score of six objective metrics. RESULTS: All 24 subjects (mean age, 29.8 years) completed the study. For nighttime driving, the adjusted mean differences in Z score (95% confidence interval) between test and control 1 and between test and control 2 were 0.069 (-0.045 to +0.183) and 0.117 (0.003 to 0.231), respectively. For daytime driving, mean differences were 0.101 (-0.013 to +0.216) between test and control 1 and 0.044 (-0.070 to +0.158) between test and control 2. Results demonstrated noninferiority of the test lens relative to controls for nighttime and daytime driving performance using a noninferiority margin of -0.25 Z score. Noninferiority was also demonstrated on all logMAR and contrast threshold testing. No adverse events were reported during the study. CONCLUSIONS: Study results revealed no evidence of concerns with either driving performance or vision while wearing photochromic contact lenses.

Safety of soft contact lenses in children: retrospective review of six randomized controlled trials of myopia control.

PURPOSE: To examine the rate and types of ocular adverse events among children wearing soft contact lenses. METHODS: This study is a retrospective review of ocular adverse event data from six randomized controlled trials among a total of 581 myopic children (aged 7-15 years at baseline) administered daily disposable hydrogel contact lenses (etafilcon A). RESULTS: During 816 patient years of contact lens wear, no significant or serious ocular adverse events were reported. A total of 86 non-significant ocular adverse events occurred in 53 children. The crude rate of ocular adverse events was 10.6 per 100 patient years with the estimated pooled incidence being 8.9 per 100 patient years (95% CI: 4.5-17.4). Two asymptomatic corneal infiltrative events were reported (both non-significant), which is an incidence of 0.3 (95% CI: 0.1-0.9) per 100 patient years. The most common ocular adverse events (n) were slit-lamp findings of Grade 2 or less requiring treatment (26), unspecified conjunctivitis (14), and allergic conjunctivitis (13). No cases of microbial keratitis were observed. Of the 86 adverse events, 37 were classified as highly likely or possibly lens-related, giving a crude incidence of 4.5 per 100 patient years for contact lens-related events. The crude incidence of ocular adverse events among spectacle wearers was 1.8 per 100 patient years. CONCLUSION: These data suggest that daily disposable soft contact lenses can be safely worn by children. Additional studies will be needed to precisely quantify the adverse event rate of soft contact lenses in normal clinical practice.

A contra-lateral comparison of the visual effects of a photochromic vs. non-photochromic contact lens.

PURPOSE: To compare the effects of a photochromic contact lens vs. a non-photochromic control lens on visual function. METHODS: A subject-masked, prospective contralateral eye design was used. Sixty-one subjects were enroled based on age (using a 2:1 allocation ratio for ages 18-39 and 40-65 years, respectively). The study lenses were senofilcon A with photochromic additive (Test) that filtered over the entire lens, compared to a non-photochromic Control with no tint. The Test lens was partially activated during testing with a steady-state transmittance of approximately 62%. Eligible subjects were tested using both study lenses, with Test and Control lens randomized by eye. Five visual function outcomes were tested: photostress recovery (PSR), glare disability (GD), glare discomfort (GDC), chromatic contrast (CC) and vernier acuity (VA). Iris colour and macular pigment density were assessed as control variables. PSR was measured as the time needed to recover sight of a target after an intense xenon flash exposure; GD was evaluated as the energy needed to veil a central target by a surrounding xenon annulus; GDC was measured using bio-imaging of the squint response and by self-report using a 9-item Likert scale; CC was measured as thresholds for a yellow grating target superposed on a 460-nm background; VA was determined by measuring vernier offsets of light lines through apertures. RESULTS: Based on our stimulus conditions, PSR was 43% faster using the Test vs. the Control. The eye wearing the Test had 38% less squint (GDC) compared to the Control. GD was improved by 36% in the Test vs. Control and CC was enhanced by 48% with the Test. There was no significant difference in VA. CONCLUSIONS: There was a beneficial influence on visual function when comparing the photochromic with the non-photochromic contact lens. This benefit was seen specifically with respect to PRT, GDC, GD and CC thresholds.

Design and analysis of Bayesian adaptive crossover trials for evaluating contact lens safety and efficacy.

A crossover study, also referred to as a crossover trial, is a form of longitudinal study. Subjects are randomly assigned to different arms of the study and receive different treatments sequentially. While there are many frequentist methods to analyze data from a crossover study, random effects models for longitudinal data are perhaps most naturally modeled within a Bayesian framework. In this article, we introduce a Bayesian adaptive approach to crossover studies for both efficacy and safety endpoints using Gibbs sampling. Using simulation, we find our approach can detect a true difference between two treatments with a specific false-positive rate that we can readily control via the standard equal-tail posterior credible interval. We then illustrate our Bayesian approaches using real data from Johnson & Johnson Vision Care, Inc. contact lens studies. We then design a variety of Bayesian adaptive predictive probability crossover studies for single and multiple continuous efficacy endpoints, indicate their extension to binary safety endpoints, and investigate their frequentist operating characteristics via simulation. The Bayesian adaptive approach emerges as a crossover trials tool that is useful yet surprisingly overlooked to date, particularly in contact lens development.

Lid Wiper Epitheliopathy in Soft Contact Lens Wearers.

PURPOSE: To evaluate lid wiper epitheliopathy (LWE) in soft contact lens (SCL) wearers on initial presentation and after using various SCL and solution combinations. METHODS: LWE was assessed in 253 habitual SCL wearers who attended a screening visit at one of three study sites. LWE was assessed using lissamine green and sodium fluorescein dyes (Korb scale); a final LWE grade was calculated as the averaged LWE grade of the two dyes. Eligible habitual wearers continued into the four study periods, during which they wore one of three SCL types (etafilcon A, galyfilcon A, or senofilcon A) while using each of four care solutions for 10 to 14 days in randomized order. Statistical analyses were performed using linear mixed models, testing for differences in LWE for subject characteristics and between three multipurpose (MPS) test solutions (BioTrue, OPTI-FREE PureMoist, RevitaLens OcuTec) compared to a hydrogen peroxide (Clear Care) control solution. RESULTS: LWE was present in 85% of habitual SCL wearers. LWE was not different for age (p = 0.28), sex (p = 0.99), race (p = 0.34), and comfort (p = 0.38) and not correlated with refractive error (r = 0.07). LWE was lower in habitual senofilcon A wearers (least-squares (LS) mean ± SE = 0.82 ± 0.19) compared to wearers of lotrafilcon B (1.34 ± 0.20; p < 0.02), comfilcon A (1.41 ± 0.21; p < 0.01), and other (1.18 ± 0.16; p < 0.03). Two hundred three participants completed all four study solutions with their assigned lens type; LWE was not different between the MPSs compared to the peroxide control solution across lens materials, except for less LWE for BioTrue (0.88 ± 0.17) versus Clear Care for participants wearing galyfilcon A (1.11 ± 0.18; p < 0.01). CONCLUSIONS: On initial presentation, LWE was present in 85% of habitual wearers and found to be independent of age, sex, race, comfort, and refractive error but dependent on habitual SCL type. There were no clinically meaningful differences in LWE between the MPSs and hydrogen peroxide solution for the three lens types studied.

Coefficient of Friction of Human Corneal Tissue.

PURPOSE: A novel property evaluation methodology was used to determine the elusive value for the human corneal coefficient of friction (CoF). METHODS: Using a microtribometer on 28 fresh human donor corneas with intact epithelia, the CoF was determined in 4 test solutions (≥5 corneas/solution): tear-mimicking solution (TMS) in borate-buffered saline (TMS-PS), TMS in phosphate-buffered saline (TMS-PBS), TMS with HEPES-buffered saline (TMS-HEPES), and tear-like fluid in PBS (TLF-PBS). RESULTS: Mean (SD) CoF values ranged from 0.006 to 0.015 and were 0.013 (0.010) in TMS-PS, 0.006 (0.003) in TMS-PBS, 0.014 (0.005) in TMS-HEPES, and 0.015 (0.009) in TLF-PBS. Statistically significant differences were shown for TMS-PBS versus TLF (P = 0.0424) and TMS-PBS versus TMS-HEPES (P = 0.0179), but not for TMS-PBS versus TMS-PS (P = 0.2389). CONCLUSIONS: Successful measurement of the fresh human corneal tissue CoF was demonstrated, with values differing in the evaluated buffer solutions, within this limited sample size.

Resultant vertical prism in toric soft contact lenses.

PURPOSE: Rotational stability of toric soft contact lenses (TSCLs) is achieved using a range of designs. Designs utilising prism or peripheral ballast may result in residual prism in the optic zone. This study quantifies the vertical prism in the central 6mm present in TSCLs with various stabilisation methods. METHOD: Vertical prism was computed using published refractive index and vertical thickness changes in the central optic zone on a full lens thickness map. Thickness maps were measured using scanning transmission microscopy. Designs tested were reusable, silicone hydrogel and hydrogel TSCLs: SofLens(®) Toric, PureVision(®)2 for Astigmatism, PureVision(®) Toric, Biofinity(®) Toric, Avaira(®) Toric, clariti(®) toric, AIR OPTIX(®) for ASTIGMATISM and ACUVUE OASYS(®) for ASTIGMATISM; with eight parameter combinations for each lens (-6.00DS to +3.00DS, -1.25DC, 90° and 180° axes). RESULTS: All TSCL designs evaluated had vertical prism in the optic zone except one which had virtually none (0.01Δ). Mean prism ranged from 0.52Δ to 1.15Δ, with three designs having prism that varied with sphere power. Vertical prism in ACUVUE OASYS(®) for ASTIGMATISM was significantly lower than all other TSCLs tested. CONCLUSIONS: TSCL designs utilising prism-ballast and peri-ballast for stabilisation have vertical prism in the central optic zone. In monocular astigmats fitted with a TSCL or those wearing a mix of toric designs, vertical prism imbalance could create or exacerbate disturbances in binocular vision function. Practitioners should be aware of this potential effect when selecting which TSCL designs to prescribe, particularly for monocular astigmats with pre-existing binocular vision anomalies, and when managing complaints of asthenopia in monocular astigmats.

Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses.

BACKGROUND AND OBJECTIVE: Optimal endoscopic hemostasis remains undetermined. This was a systematic review of contemporary methods of endoscopic hemostasis for patients with bleeding ulcers that exhibited high-risk stigmata. SETTING: Randomized trials that evaluated injection, thermocoagulation, clips, or combinations of these were evaluated from MEDLINE, EMBASE, and CENTRAL (1990-2006). PATIENTS: A total of 4261 patients were evaluated. OUTCOMES: Outcomes were rebleeding (primary), surgery, and mortality (secondary). Summary statistics were determined; publication bias and heterogeneity were sought by using funnel plots or by subgroup analyses and meta-regression. RESULTS: Forty-one trials assessed 4261 patients. All endoscopic therapies decreased rebleeding versus pharmacotherapy alone, including sole intravenous (IV) proton pump inhibition (PPI) (OR 0.56 [95% CI, 0.34-0.92]); only one trial assessed high-dose IV PPI. Injection alone was inferior compared with other methods, except for thermal hemostasis (OR 1.02 [95% CI, 0.74-1.40]), with a strong trend of increased rebleeding if 1 injectate is used rather than 2 (OR 1.40 [95% CI, 0.95-2.05]). Injection followed by thermal therapy did not decrease rebleeding compared with clips (OR 0.82 [95% CI, 0.28-2.38]) or thermal therapy alone (OR 0.79 [95% CI, 0.24-2.62]). Subgroup analysis, however, suggested that injection followed by thermal therapy was superior to thermal therapy alone. Clips were superior to thermal therapy (OR 0.24 [95% CI, 0.06-0.95]) but, when followed by injection, were not superior to clips alone (OR 1.30 [95% CI, 0.36-4.76]). Surgery or mortality was not altered in most comparisons. CONCLUSIONS: All endoscopic treatments are superior to pharmacotherapy alone; only 1 study assessed high-dose IV PPI. Optimal endoscopic therapies include thermal therapy or clips, either alone or in combination with other methods. Additional data are needed that compare injection followed by thermal therapy to clips alone or clips combined with another method.

Do proton-pump inhibitors confer additional gastrointestinal protection in patients given celecoxib?

OBJECTIVE: Celecoxib has a superior upper-gastrointestinal (GI) safety profile compared with nonselective nonsteroidal antiinflammatory drugs (NS-NSAIDs). It is unclear whether the utilization of a proton-pump inhibitor (PPI) with celecoxib confers additional protection in elderly patients. We assessed the association between GI hospitalizations and use of celecoxib with a PPI versus celecoxib alone, and NS-NSAIDs with a PPI or NS-NSAIDs alone in elderly patients. METHODS: We conducted a population-based retrospective cohort study using the government of Quebec health services administrative databases. Elderly patients were included at their first dispensing date for celecoxib or an NS-NSAID between April 1999 and December 2002. Prescriptions were separated into 4 groups: celecoxib, celecoxib plus PPI, NS-NSAIDs, and NS-NSAIDs plus PPI. Cox regression models with time-dependent exposure were used to compare the hazard rates of GI hospitalization between the 4 groups adjusting for patient characteristics at baseline. RESULTS: There were 1,161,508 prescriptions for celecoxib, 360,799 for celecoxib plus PPI, 715,176 for NS-NSAIDs, and 148,470 for NS-NSAIDs plus PPI. The adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) were 0.69 (0.52-0.93) for celecoxib plus PPI versus celecoxib, 0.98 (0.67-1.45) for NS-NSAIDs plus PPI versus celecoxib, and 2.18 (1.82-2.61) for NS-NSAIDs versus celecoxib. Subgroup analyses showed that use of a PPI with celecoxib may be beneficial in patients ages >/=75 years but was not better than celecoxib alone among those ages 66-74 years (HR 0.98, 95% CI 0.63-1.52). CONCLUSION: Addition of a PPI to celecoxib conferred extra protection for patients ages >/=75 years. PPI did not seem necessary with celecoxib for patients ages 66-74 years.

Association between nonnaproxen NSAIDs, COX-2 inhibitors and hospitalization for acute myocardial infarction among the elderly: a retrospective cohort study.

PURPOSE: To evaluate the association between rofecoxib, celecoxib, diclofenac, and ibuprofen and the risk of hospitalization for acute myocardial infarction (AMI) in an elderly population. METHODS: We conducted a retrospective cohort study, using data from the government of Quebec health insurance agency databases, among patients 65-80 years of age who filled a prescription for any of the study drugs during 1999-2002. Cox regression models with time-dependent exposure were used to compare the incidence rates of hospitalization for AMI adjusting for patients' baseline characteristics. Analyses stratified by dose and number of supplied days were also conducted. RESULTS: At the index date, a total of 91 062 patients were taking rofecoxib, 127 928 celecoxib, 49 193 diclofenac, and 15 601 ibuprofen. The adjusted hazard ratio (HR) (95%CI) of hospitalization for AMI were: celecoxib versus rofecoxib: 0.90 (0.79, 1.01); ibuprofen versus rofecoxib: 0.95 (0.65, 1.37); diclofenac versus rofecoxib: 1.01 (0.84, 1.22). In secondary analyses based on intended duration of use, neither COX-2 selective inhibitor was associated with a higher risk than ibuprofen or diclofenac. The unadjusted risk of AMI for all NSAIDs increased with dose. In the direct two way adjusted comparison of each NSAID stratified by dose, the only statistically significant difference was with rofecoxib >25 mg/day versus celecoxib >200 mg/day. CONCLUSION: In this study there was no difference between AMI occurrence in elderly patients taking rofecoxib or celecoxib at recommended doses for chronic indications versus those taking ibuprofen/diclofenac. However, the risk of AMI was higher among patients using higher doses of rofecoxib (>25 mg/day) compared to patients using higher doses of celecoxib (>200 mg/day).