Medication adherence to injectable glucagon-like peptide-1 (GLP-1) receptor agonists dosed once weekly vs once daily in patients with type 2 diabetes: A meta-analysis.

BACKGROUND: Suboptimal medication adherence has been associated with increased resource utilisation and mortality among patients with type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly important in the treatment of T2D. However, medications in this class differ considerably in their dosing frequency, which may impact adherence. We sought to perform a meta-analysis to compare adherence to injectable GLP-1RAs dosed once weekly vs once daily in patients with T2D. METHODS: Medline and Scopus were searched from 1/2005 to 7/2020 using keywords and MeSH terms pertaining to adherence and GLP-1RAs. Studies of adults with T2D were included if they compared adherence (as measured by proportion of days covered [PDC]) to injectable GLP-1RAs dosed once weekly vs once daily. A meta-analysis of non-overlapping studies was performed to evaluate the primary outcome of non-adherence, defined as the proportion of patients with a PDC < 80. RESULTS: A total of 7 studies evaluating 75 159 patients (range: 2886-30 097) with T2D were included. The follow-up periods of included studies ranged from 6 to 12 months. Injectable GLP-1RAs dosed once weekly were either dulaglutide, albiglutide or exenatide extended release; while liraglutide was the injectable once daily agent evaluated in all included studies. Upon meta-analysis, once weekly GLP-1RA dosing was associated with an 11% lower risk of non-adherence compared to once daily dosing (risk ratio = 0.89; 95% confidence interval = 0.83-0.95; I2  = 89%). CONCLUSION: Once weekly dosing of injectable GLP-1RAs was associated with better adherence vs once daily dosing among patients with T2D. These findings coupled with the known detrimental consequences of non-adherence suggest that dosing frequency is an important factor to consider when selecting a GLP-1RA.

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.

The Effect of a Photochromic Contact Lens on Visual Function Indoors: A Randomized, Controlled Trial.

SIGNIFICANCE: Photochromic soft contact lenses contain light-sensitive additives that allow them to darken when exposed to ultraviolet or violet light. One question, however, is whether the lenses influence vision indoors (minimally activated). In this study, we found that the minimally activated lenses improved many aspects of visual function under bright light. PURPOSE: Photochromic contact lenses were designed to darken when exposed to outdoor sunlight. The filtering that results improves visual function under bright light conditions. Not all bright light exposures occur outdoors. In this study, we tested whether a photochromic contact lens improved visual function under conditions where the lens was minimally activated (i.e., no more than it normally would be in an indoor environment). METHODS: A subject-masked contralateral design was used comparing a photochromic contact lens randomized to one eye against a nonphotochromic contact in the other eye of the same subject. Sixty subjects (mean = 34.90 ± 11.24 years) were tested. The primary endpoints consisted of four visual function outcomes: photostress recovery, glare disability, glare discomfort, and chromatic contrast. Photostress recovery was quantified by measuring the time needed to recover visual acquisition of a grating target after 5 seconds of an intense xenon white flash exposure; glare disability was evaluated as the energy in a surrounding xenon white annulus necessary to veil a central grating target; and glare discomfort was assessed using bioimaging of the squint response. Chromatic contrast was measured as thresholds for a green-yellow (580 nm) grating target superposed on a blue (460 nm) background. RESULTS: The minimally activated photochromic contact demonstrated improved visual performance compared with the nonphotochromic control across all visual functions tested (P < .01). CONCLUSIONS: Even under conditions of exiguous activation (e.g., as would be expected indoors or while driving at night), a photochromic contact will improve many of the more deleterious aspects of bright light.

Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis-B or -C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long-term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high-risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis. METHODS: Previously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC-TC. After one course of trans-arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC-TC suspended in granulocyte-macrophage colony stimulating factor were administered. Patients were monitored for eight weeks. RESULTS: HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA. CONCLUSION: Autologous DC-TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned.

Unexpected vision performance with photochromic contact lenses in normal and low light conditions: An analysis of two randomized trials.

PURPOSE: Evaluate the performance of a photochromic contact lens in various lighting conditions throughout the day, including those indoor and outdoor environments where the photochromic contact lens is in a less active or inactive state. METHODS: Data from two clinical trials of a photochromic contact lens were analyzed to evaluate its performance in various light environments. Both studies involved a photochromic test lens (ACUVUE® OASYS with Transitions™ Light Intelligent Technology™) and a similar non-photochromic control lens (ACUVUE® OASYS 2-week with HYDRACLEAR® PLUS). The studies were both multi-visit, multi-site, 2-treatment by 3-period randomized crossover (i.e., Test/Control/Control or Control/Test/Test) dispensing studies, with follow-up visits after each 2-week dispensing period. RESULTS: A total of 250 subjects were dispensed lenses across both studies, of which 237 total subjects completed. In situations where exposure to an activating light source is common (e.g., outdoors), the Test lens was preferred nearly 6:1 over the control lens. In situations where exposure to an activating light source is less common - indoors, driving at night, using digital devices -, the Test lens was still preferred over the control lens by margins of 4:1, nearly 4:1, and over 3:1 respectively. The Test lens was superior with respect to quality of vision, ability to see comfortably, clarity of vision, reduction of squinting while using computers and reduction of bright light while driving at night. CONCLUSION: The photochromic test contact lens was rated superior to a non-photochromic control lens in environmental situations where the lens is in a less active or inactive state.

Lens fitting and subjective acceptance of senofilcon A with photochromic additive on a neophyte population.

PURPOSE: To determine the proportion of contact lens neophytes that can be successfully fitted with a photochromic contact lens, and to survey subjective performance outcomes compared to habitual spectacles. It was hypothesized that at least 50 % of lens fits would be successful. METHODS: Eleven sites enrolled contact lens neophytes with up-to-date spectacles. Subjects were fitted bilaterally with a photochromic Test contact lens (ACUVUE® OASYS with Transitions™) for one month of daily, reusable wear. Follow-up visits occurred at 1 week, 2 weeks (lenses replaced), and at 4 weeks after initial dispensing. The investigator judged lens fitting success based on overall assessment of physiology, mechanical fitting, comfort, vision, and handling at the 4-week visit. Following this visit, subjects returned to wearing habitual spectacles for one week and evaluated the performance of the study lens compared to their spectacles. RESULTS: From a total of 127 subjects who were dispensed contact lenses, 105 completed the study per protocol (mean age: 25.5 ± 5.9 years; 57 % female; 80.0 % Caucasian; 71 % with dark iris color). Investigators judged that 97 % of the contact lenses were fitted successfully after 4 weeks of wear; thus, the primary hypothesis was met. Among per-protocol subjects, 60 % reported better vision outdoors, 53 % better vision in changing lighting conditions, 62 % less squinting, and 66 % being less often bothered by bright light. Additionally, 95 % would recommend the lens to others, and 71 % would recommend their eye care practitioner if offered the lens. CONCLUSION: Greater than 95 % of subjects were successfully fitted with the photochromic contact lens based on professional judgement of physiology, mechanical fitting, comfort, vision, and handling. Subjects new to contact lens wear expressed positive opinions for the study contact lenses compared to their up-to-date spectacles.

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.

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.

Unexpected vision performance with photochromic contact lenses in normal and low light conditions: An analysis of two randomized trials / Rendimiento visual inesperado con lentes de contacto fotocromáticos en condiciones normales y de poca luz: un análisis de dos ensayos aleatorios

Purpose: Evaluate the performance of a photochromic contact lens in various lighting conditions throughout the day, including those indoor and outdoor environments where the photochromic contact lens is in a less active or inactive state. Methods: Data from two clinical trials of a photochromic contact lens were analyzed to evaluate its performance in various light environments. Both studies involved a photochromic test lens (ACUVUE® OASYS with Transitions™ Light Intelligent Technology™) and a similar non-photochromic control lens (ACUVUE® OASYS 2-week with HYDRACLEAR® PLUS). The studies were both multi-visit, multi-site, 2-treatment by 3-period randomized crossover (i.e., Test/Control/Control or Control/Test/Test) dispensing studies, with follow-up visits after each 2-week dispensing period. Results: A total of 250 subjects were dispensed lenses across both studies, of which 237 total subjects completed. In situations where exposure to an activating light source is common (e.g., outdoors), the Test lens was preferred nearly 6:1 over the control lens. In situations where exposure to an activating light source is less common – indoors, driving at night, using digital devices –, the Test lens was still preferred over the control lens by margins of 4:1, nearly 4:1, and over 3:1 respectively. The Test lens was superior with respect to quality of vision, ability to see comfortably, clarity of vision, reduction of squinting while using computers and reduction of bright light while driving at night. Conclusion: The photochromic test contact lens was rated superior to a non-photochromic control lens in environmental situations where the lens is in a less active or inactive state.(AU)

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

Prevalence of potentially neuropathic Campylobacter jejuni strains on commercial broiler chicken products.

Campylobacteriosis is the most common antecedent infection leading to the development of inflammatory neuropathies including Guillain Barré syndrome (GBS) and Miller Fisher syndrome (MFS), with alterations in surface proteins and genetic polymorphisms conferring increased risk. Poultry is the most common source of C. jejuni infection in industrialized countries, including the US. There are no data on the prevalence on consumer poultry products of various strains of C. jejuni, including those hypothesized to be associated with neuropathy. To study this, C. jejuni was isolated from fresh broiler chicken products purchased from grocery stores in the Baltimore area. LOS subtypes and specific genetic polymorphisms were determined by PCR and DNA sequencing. The observed relative proportions of LOS subtypes and genetic polymorphisms in the cstII gene (encoding bacterial sialyltransferases involved in LOS synthesis in C. jejuni) were characterized and compared to those reported in published studies of patients with GBS, MFS and uncomplicated enteritis. Commercial poultry products carry a relatively high prevalence of C. jejuni strains that have been associated with neuropathic sequelae. The relative proportions of LOS classes in poultry isolates were similar to those reported in isolates from human enteritis cases, and in some instances also similar to isolates from patients diagnosed with neuropathic disease. In terms of cstII polymorphisms, there were also similarities between isolates from poultry and those from patients with GBS and MFS.