Impossibility to eliminate observer effect in the assessment of adherence in clinical trials.

PURPOSE: To utilize the Travoprost Dosing Aid (DA) in the assessment of patient medication adherence, while also determining whether or not altering the functionality of the DA in three randomized subject groups can reduce observer effect. METHODS: Forty-five subjects were randomized into three groups: two with monitored DAs and one without monitoring. One group of subjects was given a DA that both monitored drop usage and had visual and audible alarms, while the other monitored group included subjects given a DA that had no alarms but continued to monitor drop usage. The third group was given a DA that had no alarm reminders or dose usage monitoring. Subjects were informed that some monitors would not be functional, in an attempt to reduce observer effect, or the effect of being monitored on subject behavior and adherence. A six-item questionnaire was also utilized to assess how the subjects felt about their adherence and DA use. RESULTS: The overall adherence rates were found to be 78% in the fully functional group (95% confidence interval: 70-88) and 76% in the no alarms group (95% confidence interval: 65-89). No association was seen between questionnaire response and medication adherence. The patients in the DA group without alarms had a significantly higher odds ratio of medication adherence if they reported on the questionnaire that using the DA did affect how much they used their drops. CONCLUSION: Though the use of DA was expected to reveal different rates of adherence depending on the functionality of the DA between groups, patients with a nonfunctioning DA did not have a significant difference in medication adherence compared to those given a fully functional DA. This supports that an observer effect was not reduced despite these interventions, and that the subjects adhered to taking their medications as if they had a functioning DA and were being monitored

Non-adherence to eye care in people with diabetes

Objective Evaluate individual factors that impact adherence to eye care follow-up in patients with diabetes. Design and methods A 4-year retrospective chart review was conducted for 1968 patients with diabetes over age 40 from an urban academic center. Data collected included demographics, insurance, visual acuity, smoking status, medications, dates of dilated fundus examinations (DFE), and reported hemoglobin A1C and blood glucose levels. The primary outcome was timely DFE follow-up adherence following the initial eye exam visit. Results Overall, 41.6% of patients adhered to initial follow-up eye care recommendations. Multivariable analysis demonstrated that patients with severe diabetic retinopathy (DR) were more adherent than patients with mild DR (OR 1.86). Other variables associated with increased adherence were visual impairment and reported A1C or blood glucose. Smoking was associated with decreased adherence. Ethnicity and insurance were also significantly associated with adherence. Longitudinal follow-up rates were influenced by additional factors, including ethnicity and neighborhood deprivation index. Conclusions Patients with moderate to severe DR and/ or visual impairment were more likely to adhere to timely DFE follow-up. This could relate to the presence of visual symptoms and/or other systemic manifestations of diabetes. Smokers were less likely to adhere to timely DFE follow-up. One hypothesis is patients who smoke have other symptomatic health problems which patients prioritize over asymptomatic ocular disorders. In order to reduce vision loss from DR, practitioners should be aware that patients with mild and moderate DR, patients with normal vision, and smokers are at greater risk for poor follow-up eye care adherence. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved

Factors contributing to nonadherence to follow-up appointments in a resident glaucoma clinic versus primary eye care clinic.

PURPOSE: To determine the rate of adherence to follow-up appointment recommendations in a resident glaucoma clinic with no mechanism for reminders, compared to a resident cataract and primary eye care (CPEC) clinic in which telephone reminders were used, and to identify factors that contribute to adherence in each patient group. METHODS: This retrospective cohort study included subjects in the CPEC clinic who received telephone reminders and those in the glaucoma clinic who did not. Each sample was selected to have a similar proportion of follow-up recommendations for 1, 3, and 6 months. Subjects were considered adherent if they returned within a specified timeframe. RESULTS: A total of 144 subjects from the glaucoma clinic and 151 subjects from the CPEC clinic were included. There was no significant difference between follow-up adherence rates of patients who received telephone reminders and those who did not (odds ratio [OR] =1.35, 95% confidence interval [CI] 0.79-2.32, P=0.28). Patients who were on more than two ocular medications were more likely to return for follow-up (OR=3.11, 95% CI 1.53-6.35, P=0.0018). Subjects between the ages 50 and 80 years were more likely to be adherent compared to their younger and older peers (P=0.02). CONCLUSION: The follow-up adherence of patients in a CPEC clinic who received telephone reminders was similar to patients in a glaucoma clinic who did not receive any intervention to increase their adherence. Younger (⩽50 years old) and elderly (⩾80 years old) subjects, as well as patients using less than two glaucoma medications, were less likely to adhere to their follow-up appointments

Diabetes eye screening in urban settings serving minority populations: detection of diabetic retinopathy and other ocular findings using telemedicine.

IMPORTANCE: The use of a nonmydriatic camera for retinal imaging combined with the remote evaluation of images at a telemedicine reading center has been advanced as a strategy for diabetic retinopathy (DR) screening, particularly among patients with diabetes mellitus from ethnic/racial minority populations with low utilization of eye care. OBJECTIVE: To examine the rate and types of DR identified through a telemedicine screening program using a nonmydriatic camera, as well as the rate of other ocular findings. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study (Innovative Network for Sight [INSIGHT]) was conducted at 4 urban clinic or pharmacy settings in the United States serving predominantly ethnic/racial minority and uninsured persons with diabetes. Participants included persons aged 18 years or older who had type 1 or 2 diabetes mellitus and presented to the community-based settings. MAIN OUTCOMES AND MEASURES: The percentage of DR detection, including type of DR, and the percentage of detection of other ocular findings. RESULTS: A total of 1894 persons participated in the INSIGHT screening program across sites, with 21.7% having DR in at least 1 eye. The most common type of DR was background DR, which was present in 94.1% of all participants with DR. Almost half (44.2%) of the sample screened had ocular findings other than DR; 30.7% of the other ocular findings were cataract. CONCLUSIONS AND RELEVANCE: In a DR telemedicine screening program in urban clinic or pharmacy settings in the United States serving predominantly ethnic/racial minority populations, DR was identified on screening in approximately 1 in 5 persons with diabetes. The vast majority of DR was background, indicating high public health potential for intervention in the earliest phases of DR when treatment can prevent vision loss. Other ocular conditions were detected at a high rate, a collateral benefit of DR screening programs that may be underappreciated

A Randomized Trial to Improve Adherence to Follow-up Eye Examinations Among People With Glaucoma

INTRODUCTION: Appointment nonadherence is common among people with glaucoma, making it difficult for eye care providers to monitor glaucoma progression. Our objective was to determine whether the use of patient navigators, in conjunction with social worker support, could increase adherence to recommended follow-up eye appointments. METHODS: A randomized, controlled trial evaluated the effectiveness of an intervention that used patient navigators and social workers to improve patient adherence to follow-up eye care compared with usual care. Participants with glaucoma and other eye diseases (N = 344) were identified at primary care clinics in community settings through telemedicine screening of imaging and then randomized to enhanced intervention (EI) or usual care (UC). Data on participants\u27 visits with local ophthalmologists were collected for up to 3 years from randomization. Groups were compared for timely attendance at the first visit with the local ophthalmologist and adherence to recommended follow-up visits. RESULTS: Timely attendance at the first visit was higher for EI than UC (74.4% vs 39.0%; average relative risk [aRR] = 1.85; 95% CI, 1.51-2.28; P \u3c .001). Rates of adherence to recommended annual follow-up during year 1 were 18.6% in the EI group and 8.1% in the usual care group (aRR = 2.08; 95% CI, 1.14-3.76; P = .02). The aRR across years 2 and 3 was 3.92 (95% CI, 1.24-12.43; P = .02). CONCLUSION: An intervention using patient navigators and social workers doubled the rate of adherence to annual recommended follow-up eye care compared with usual care in community settings, and was effective at increasing connections with local ophthalmologists. Interventions to further improve long-term adherence are needed

The Human Retinoblastoma Gene Is Imprinted

Genomic imprinting is an epigenetic process leading to parent-of-origin–specific DNA methylation and gene expression. To date, ∼60 imprinted human genes are known. Based on genome-wide methylation analysis of a patient with multiple imprinting defects, we have identified a differentially methylated CpG island in intron 2 of the retinoblastoma (RB1) gene on chromosome 13. The CpG island is part of a 5′-truncated, processed pseudogene derived from the KIAA0649 gene on chromosome 9 and corresponds to two small CpG islands in the open reading frame of the ancestral gene. It is methylated on the maternal chromosome 13 and acts as a weak promoter for an alternative RB1 transcript on the paternal chromosome 13. In four other KIAA0649 pseudogene copies, which are located on chromosome 22, the two CpG islands have deteriorated and the CpG dinucleotides are fully methylated. By analysing allelic RB1 transcript levels in blood cells, as well as in hypermethylated and 5-aza-2′-deoxycytidine–treated lymphoblastoid cells, we have found that differential methylation of the CpG island skews RB1 gene expression in favor of the maternal allele. Thus, RB1 is imprinted in the same direction as CDKN1C, which operates upstream of RB1. The imprinting of two components of the same pathway indicates that there has been strong evolutionary selection for maternal inhibition of cell proliferation

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs

MicroRNAs (miRNAs) are small ∼22-nt RNAs that are important regulators of posttranscriptional gene expression. Since their initial discovery, they have been shown to be involved in many cellular processes, and their misexpression is associated with disease etiology. Currently, nearly 2,800 human miRNAs are annotated in public repositories. A key question in miRNA research is how many miRNAs are harbored by the human genome. To answer this question, we examined 1,323 short RNA sequence samples and identified 3,707 novel miRNAs, many of which are human-specific and tissue-specific. Our findings suggest that the human genome expresses a greater number of miRNAs than has previously been appreciated and that many more miRNA molecules may play key roles in disease etiology

Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility

Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with kno