Listening Sessions to Shape the Innovative NIH ComPASS Common Fund Program to Advance Health Equity.

The National Institutes of Health (NIH) recognized the need for a research program to address the underlying structural factors that impact health. To inform the development of the NIH Common Fund Community Partnerships to Advance Science for Society (ComPASS) Program, NIH obtained input through community listening sessions. Through its design, ComPASS recognizes the essential role of community organizations as the lead in addressing persistent structural and social challenges to accelerate progress toward advancing health equity. (Am J Public Health. Published online ahead of print April 18, 2024:e1-e5. https://doi.org/10.2105/AJPH.2024.307656).

Iridotomy to slow progression of visual field loss in angle-closure glaucoma.

BACKGROUND: Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. For example, contact between the iris and lens at the pupillary margin creates a pupillary block that increases resistance to aqueous outflow. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy ('iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber, which is achieved by creating a hole in the iris using laser. Iridotomy is used to treat patients with primary angle-closure glaucoma, patients with primary angle-closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). However, the effectiveness of iridotomy on slowing progression of visual field loss is uncertain. OBJECTIVES: To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle-closure, and primary angle-closure suspect. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 10), which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the WHO ICTRP. The date of the most recent search was 10 October 2021. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that compared iridotomy with no iridotomy in primary angle-closure suspects, people with primary angle-closure, or people with primary angle-closure glaucoma in one or both eyes were eligible. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach. MAIN RESULTS: We identified four studies (3086 eyes of 1543 participants) that compared iridotomy with no iridotomy in participants (range of mean age 59.6 to 62.9 years) who were primary angle-closure suspects from China, Singapore, or the UK. Study investigators randomized one eye of each participant to iridotomy and the other to no iridotomy. Two studies provided long-term (five or more years) results. We judged the certainty of the evidence as moderate to low across the prespecified outcomes, downgrading for high risk of bias (e.g. performance and detection biases) and imprecision of results. Meta-analyses of data from two studies suggest that iridotomy probably results in little to no difference in IOP compared with no iridotomy at one year (mean difference (MD) 0.04 mm Hg, 95% confidence interval (CI) -0.17 to 0.24; I2 = 65%; 2598 eyes of 1299 participants; moderate certainty evidence) and five years (MD 0.12 mm Hg, 95% CI -0.11 to 0.35; I2 = 0%; 2016 eyes of 1008 participants), and in best-corrected visual acuity measured as logMAR at one year (MD 0.00, 95% CI -0.01 to 0.01; I2 = 69%; 2596 eyes of 1298 participants; moderate certainty evidence) and five years (MD 0.01, 95% CI -0.01 to 0.03; I2 = 0%; 2002 eyes of 1001 participants). In terms of gonioscopic findings, eyes treated with iridotomy likely had wider angles in Shaffer grading scale (MD 4.93 units, 95% CI 4.73 to 5.12; I2 = 59%; 2598 eyes of 1299 participants at one year; MD 5.07, 95% CI 4.78 to 5.36; I2 = 97%; 2016 eyes of 1008 participants at five years; moderate certainty evidence) and experienced fewer peripheral anterior synechiae (PAS) than eyes that received no iridotomy at five years (risk ratio (RR) 0.41, 95% CI 0.24 to 0.67; I2 = 28%; 2 studies, 2738 eyes of 1369 participants), but the evidence was less conclusive at one year (RR 0.62, 95% CI 0.25 to 1.54; I2 = 57%; 3 studies, 2896 eyes of 1448 participants; low certainty evidence). No studies reported data on the proportion of participants with progressive visual field loss during follow-up (the primary outcome of this review), mean number of medications to control IOP, or quality of life outcomes. Low certainty evidence suggests that iridotomy may result in little to no difference in the incidence of acute angle-closure (RR 0.29, 95% CI 0.07 to 1.20; I2 = 0%; 3 studies, 3006 eyes of 1503 participants). Other ocular adverse events (e.g. eye pain, dry eye, redness of eyes, and ocular discomfort), although rare, were more common in eyes treated with iridotomy than in eyes in the control group.  AUTHORS' CONCLUSIONS: We did not find sufficient evidence to draw any meaningful conclusions on the use of iridotomy for the purpose of slowing progression of visual field loss. No study reported on progressive visual field loss, the primary outcome of this review. Although there is moderate certainty evidence that iridotomy results in improved gonioscopic findings, in is unclear if these findings translate to clinically meaningful benefits.

Analysis of neuronal injury transcriptional response identifies CTCF and YY1 as co-operating factors regulating axon regeneration.

Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons in vivo and that all neuronal subtypes are represented. This eDRG neuronal culture does not contain other non-neuronal cell types. Next, we performed RNA sequencing at different time points after in vitro axotomy. Analysis of differentially expressed genes revealed upregulation of known regeneration associated transcription factors, including Jun, Atf3 and Rest, paralleling the axon injury response in vivo. Analysis of transcription factor binding sites in differentially expressed genes revealed other known transcription factors promoting axon regeneration, such as Myc, Hif1α, Pparγ, Ascl1a, Srf, and Ctcf, as well as other transcription factors not yet characterized in axon regeneration. We next tested if overexpression of novel candidate transcription factors alone or in combination promotes axon regeneration in vitro. Our results demonstrate that expression of Ctcf with Yy1 or E2f2 enhances in vitro axon regeneration. Our analysis highlights that transcription factor interaction and chromatin architecture play important roles as a regulator of axon regeneration.

Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species.

The CCR5-specific antibody Leronlimab is being investigated as a novel immunotherapy that can suppress HIV replication with minimal side effects. Here we studied the virological and immunological consequences of Leronlimab in chronically CCR5-tropic HIV-1 infected humans (n = 5) on suppressive antiretroviral therapy (ART) and in ART-naïve acutely CCR5-tropic SHIV infected rhesus macaques (n = 4). All five human participants transitioned from daily combination ART to self-administered weekly subcutaneous (SC) injections of 350 mg or 700 mg Leronlimab and to date all participants have sustained virologic suppression for over seven years. In all participants, Leronlimab fully occupied CCR5 receptors on peripheral blood CD4+ T cells and monocytes. In ART-naïve rhesus macaques acutely infected with CCR5-tropic SHIV, weekly SC injections of 50 mg/kg Leronlimab fully suppressed plasma viremia in half of the macaques. CCR5 receptor occupancy by Leronlimab occurred concomitant with rebound of CD4+ CCR5+ T-cells in peripheral blood, and full CCR5 receptor occupancy was found in multiple anatomical compartments. Our results demonstrate that weekly, self-administered Leronlimab was safe, well-tolerated, and efficacious for long-term virologic suppression and should be included in the arsenal of safe, easily administered, longer-acting antiretroviral treatments for people living with HIV-1. Trial Registration: ClinicalTrials.gov Identifiers: NCT02175680 and NCT02355184.

Assessing bidirectional associations between cognitive impairment and late age-related macular degeneration in the Age-Related Eye Disease Study 2.

INTRODUCTION: We aimed to investigate bidirectional associations between cognitive impairment and late age-related macular degeneration (AMD). METHODS: Participants in the Age-Related Eye Disease Study 2 (AREDS2) received annual eye examinations and cognitive function testing (e.g., Modified Telephone Interview for Cognitive Status [TICS-M]). We examined bidirectional associations between cognitive impairment (e.g., a TICS-M score < 30) and late AMD at 5 and 10 years. RESULTS: Five thousand one hundred eighty-nine eyes (3157 participants; mean age 72.7 years) were analyzed and followed for a median of 10.4 years. Eyes of participants with cognitive impairment at baseline were more likely to progress to late AMD at 5 years (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.08-1.43) and 10 years (HR, 1.20; 95% CI, 1.05-1.37) than eyes of participants without cognitive impairment. Worse baseline AMD severity was not associated with developing cognitive impairment. DISCUSSION: Cognitive impairment is associated with late AMD progression in AREDS2. Our finding highlights the importance of eyecare for people with cognitive impairment.

Minimally Invasive Glaucoma Surgical Techniques for Open-Angle Glaucoma: An Overview of Cochrane Systematic Reviews and Network Meta-analysis.

IMPORTANCE: Glaucoma affects more than 75 million people worldwide. Intraocular pressure (IOP)-lowering surgery is an important treatment for this disease. Interest in reducing surgical morbidity has led to the introduction of minimally invasive glaucoma surgeries (MIGS). Understanding the comparative effectiveness and safety of MIGS is necessary for clinicians and patients. OBJECTIVE: To summarize data from randomized clinical trials of MIGS for open-angle glaucoma, which were evaluated in a suite of Cochrane reviews. DATA SOURCES: The Cochrane Database of Systematic Reviews including studies published before June 1, 2021. STUDY SELECTION: Reviews of randomized clinical trials comparing MIGS with cataract extraction alone, other MIGS, traditional glaucoma surgery, laser trabeculoplasty, or medical therapy. DATA EXTRACTION AND SYNTHESIS: Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines by one investigator and confirmed by a second. Methodologic rigor was assessed using the AMSTAR 2 appraisal tool and random-effects network meta-analyses were conducted. MAIN OUTCOMES AND MEASURES: The proportion of participants who did not need to use medication to reduce intraocular pressure (IOP) postsurgery (drop-free). Outcomes were analyzed at short-term (<6 months), medium-term (6-18 months), and long-term (>18 months) follow-up. RESULTS: Six eligible Cochrane reviews were identified discussing trabecular bypass with iStent or Hydrus microstents, ab interno trabeculotomy with Trabectome, subconjunctival and supraciliary drainage devices, and endoscopic cyclophotocoagulation. Moderate certainty evidence indicated that adding a Hydrus safely improved the likelihood of drop-free glaucoma control at medium-term (relative risk [RR], 1.6; 95% CI, 1.4 to 1.8) and long-term (RR, 1.6; 95% CI, 1.4 to 1.9) follow-up and conferred 2.0-mm Hg (95% CI, -2.7 to -1.3 mm Hg) greater IOP reduction at long-term follow-up, compared with cataract surgery alone. Adding an iStent also safely improved drop-free disease control compared with cataract surgery alone (RR, 1.4; 95% CI, 1.2 to 1.6), but the short-term IOP-lowering effect of the iStent was not sustained. Addition of a CyPass microstent improved drop-free glaucoma control compared with cataract surgery alone (RR, 1.3; 95% CI, 1.1 to 1.5) but was associated with an increased risk of vraision loss. Network meta-analyses supported the direction and magnitude of these results. CONCLUSIONS AND RELEVANCE: Based on data synthesized in Cochrane reviews, some MIGS may afford patients with glaucoma greater drop-free disease control than cataract surgery alone. Among the products currently available, randomized clinical trial data associate the Hydrus with greater drop-free glaucoma control and IOP lowering than the iStent; however, these effect sizes were small.

Photosensitizer delivery by fibrin glue: potential for bypassing the blood-brain barrier.

Fibrin glue (FG) has potential as a delivery vehicle for photosensitizer directly to the resection cavity, so it may bypass the blood-brain barrier (BBB) and increase the concentration of successfully delivered photosensitizer. A specialized form of photodynamic therapy (PDT), photochemical internalization (PCI), which involves both photosensitizer and chemotherapeutic agent internalization, can locally inhibit the growth of cells. This will allow the reduction of recurrence of malignant gliomas around surgical resection. This study will look at the efficacy of FG loaded with drugs in mediating both PDT and PCI in inhibiting 3-dimensional tumor spheroid growth in vitro. Experiments were conducted on spheroids comprised of F98 glioma cells using photosensitizer AlPcS2a and chemotherapeutic drug bleomycin (BLM). At 2-, 24-, 48-, and 72-h increments, supernatant covering an FG layer within a well was collected and replaced by fresh medium, then added to spheroid-containing wells, which contained the respective chemicals for PDT and PCI. The wells were then exposed to light treatment from a diode laser, and after, spheroid growth was monitored for a period of 14 days. Significant spheroid growth inhibition was observed in both PDT and PCI modalities, but was far greater in PCI. Additionally, complete growth suppression was achieved via PCI at the highest radiant exposure. Achieving a slow photosensitizer release, significant F98 spheroid inhibition was observed in FG-mediated PDT and PCI. The present study showed BLM-PCI was the most efficacious of the two modalities.

Development, implementation and evaluation of an online course on evidence-based healthcare for consumers.

BACKGROUND: Evidence-based healthcare (EBHC) principles are essential knowledge for patient and consumer ("consumer") engagement as research and research implementation stakeholders. The aim of this study was to assess whether participation in a free, self-paced online course affects confidence in explaining EBHC topics. The course comprises six modules and evaluations which together take about 6 h to complete. METHODS: Consumers United for Evidence-based Healthcare (CUE) designed, tested and implemented a free, online course for consumers, Understanding Evidence-based Healthcare: A Foundation for Action ("Understanding EBHC"). The course is offered through the Johns Hopkins Bloomberg School of Public Health. Participants rated their confidence in explaining EBHC topics on a scale of 1 (lowest) to 5 (highest), using an online evaluation provided before accessing the course ("Before") and after ("After") completing all six course modules. We analyzed data from those who registered for the course from May 31, 2007 to December 31, 2018 (n = 15,606), and among those persons, the 11,522 who completed the "Before" evaluation and 4899 who completed the "After" evaluation. Our primary outcome was the overall mean of within-person change ("overall mean change") in self-reported confidence levels on EBHC-related topics between "Before" and "After" evaluations among course completers. Our secondary outcomes were the mean within-person change for each of the 11 topics (mean change by topic). RESULTS: From May 31, 2007 to December 31, 2018, 15,606 individuals registered for the course: 11,522 completed the "Before" evaluation, and 4899 of these completed the "After" evaluation (i.e., completed the course). The overall mean change in self-reported confidence levels (ranging from 1 to 5) from the "Before" to "After" evaluation was 1.27 (95% CI, 1.24-1.30). The mean change by topic ranged from 1.00 (95% CI, 0.96-1.03) to 1.90 (95% CI, 1.87-1.94). CONCLUSION: Those who seek to involve consumer stakeholders can offer Understanding EBHC as a step toward meaningful consumer engagement. Future research should focus on long-term impact assessment of online course such as ours to understand whether confidence is retained post-course and applied appropriately.

Priorities and Treatment Preferences among Surgery-Naive Patients with Moderate to Severe Open-Angle Glaucoma.

PURPOSE: To explore patients' perspectives and experiences living with moderate to severe glaucoma through qualitative, semistructured interviews and to identify important benefits and risks that patients consider when choosing glaucoma treatments. DESIGN: Semistructured, in-person qualitative interviews with a convenience sample of patients seen at the Johns Hopkins Wilmer Eye Institute. PARTICIPANTS: Surgery-naive patients 21 years of age or older with moderate to severe open-angle glaucoma seeking treatment at the Wilmer Eye Institute's Glaucoma Center of Excellence between August and December 2018. METHODS: We conducted semistructured interviews with patients diagnosed with moderate to severe open-angle glaucoma, focusing on outcomes they prioritize when considering various treatment options. We used Atlas.ti software version 7.5.12 (Scientific Software Development GmbH, Berlin, Germany) to process interview transcripts and the framework approach to analyze the qualitative data. MAIN OUTCOME MEASURES: Patients' descriptions of outcomes important to them in management of moderate to severe open-angle glaucoma. RESULTS: Thirteen men and 15 women with a median age 67 years participated in the study. Compared with the mild-to-moderate glaucoma patients interviewed previously, these participants similarly emphasized (1) activities of daily living, (2) visual symptoms, (3) treatment burden, and (4) intraocular pressure (IOP) control, but unlike patients with milder disease, most related IOP control directly to (5) avoiding disease progression. Almost all (27/28) had also given significant thought to (6) surgical decision making and could describe how they would decide for or against a particular procedure. Finally, two thirds (18/28) expressed (7) significant fear and worry related to their glaucoma diagnosis. CONCLUSIONS: We identified outcomes that matter to patients who are undergoing treatment for moderate to severe glaucoma, many of which may serve as end points in clinical trials, such as functional independence in vision-dependent activities of daily living, avoidance of visual symptoms, and disease progression via maintenance of IOP control. We also observed that these patients have varied and nuanced perspectives on surgical management and its outcomes. It behooves providers and trial designers to consider these in future evaluations of new treatments for moderate to severe glaucoma.

Glycemic control and diabetic foot ulcer outcomes: A systematic review and meta-analysis of observational studies.

OBJECTIVE: To evaluate the association between glycemic control (hemoglobin A1C, fasting glucose, and random glucose) and the outcomes of wound healing and lower extremity amputation (LEA) among patients with diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS: Medline, EMBASE, Cochrane Library, and Scopus were searched for observational studies published up to March 2019. Five independent reviewers assessed in duplicate the eligibility of each study based on predefined eligibility criteria and two independent reviewers assessed risk of bias. Ameta-analysis was performed to calculate a pooled odds ratio (OR) or hazard ratio (HR) using random effects for glycemic measures in relation to the outcomes of wound healing and LEA. Subgroup analyses were conducted to explore potential source of heterogeneity between studies. The study protocol is registered with PROSPERO (CRD42018096842). RESULTS: Of 4572 study records screened, 60 observational studies met the study eligibility criteria of which 47 studies had appropriate data for inclusion in one or more meta-analyses(n = 12,604 DFUs). For cohort studies comparing A1C >7.0 to 7.5% vs. lower A1C levels, the pooled OR for LEA was 2.04 (95% CI, 0.91, 4.57) and for studies comparing A1C ≥ 8% vs. <8%, the pooled OR for LEA was 4.80 (95% CI 2.83, 8.13). For cohort studies comparing fasting glucose ≥126 vs. <126 mg/dl, the pooled OR for LEA was 1.46 (95% CI, 1.02, 2.09). There was no association with A1C category and wound healing (OR or HR). There was high risk of bias with respect to comparability of cohorts as many studies did not adjust for potential confounders in the association between glycemic control and DFU outcomes. CONCLUSIONS: Our findings suggest that A1C levels ≥8% and fasting glucose levels ≥126 mg/dl are associated with increased likelihood of LEA in patients with DFUs. A purposively designed prospective study is needed to better understand the mechanisms underlying the association between hyperglycemia and LEA.

Tea tree oil for Demodex blepharitis.

BACKGROUND: Demodex blepharitis is a chronic condition commonly associated with recalcitrant dry eye symptoms though many people with Demodex mites are asymptomatic. The primary cause of this condition in humans is two types of Demodex mites: Demodex folliculorum and Demodex brevis. There are varying reports of the prevalence of Demodex blepharitis among adults, and it affects both men and women equally. While Demodex mites are commonly treated with tea tree oil, the effectiveness of tea tree oil for treating Demodex blepharitis is not well documented. OBJECTIVES: To evaluate the effects of tea tree oil on ocular Demodex infestation in people with Demodex blepharitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 6); Ovid MEDLINE; Embase.com; PubMed; LILACS; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We used no date or language restrictions in the electronic search for trials. We last searched the databases on 18 June 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared treatment with tea tree oil (or its components) versus another treatment or no treatment for people with Demodex blepharitis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts and then full text of records to determine their eligibility. The review authors independently extracted data and assessed risk of bias using Covidence. A third review author resolved any conflicts at all stages. MAIN RESULTS: We included six RCTs (1124 eyes of 562 participants; 17 to 281 participants per study) from the US, Korea, China, Australia, Ireland, and Turkey. The RCTs compared some formulation of tea tree oil to another treatment or no treatment. Included participants were both men and women, ranging from 39 to 55 years of age. All RCTs were assessed at unclear or high risk of bias in one or more domains. We also identified two RCTs that are ongoing or awaiting publications. Data from three RCTs that reported a short-term mean change in the number of Demodex mites per eight eyelashes contributed to a meta-analysis. We are uncertain about the mean reduction for the groups that received the tea tree oil intervention (mean difference [MD] 0.70, 95% confidence interval [CI] 0.24 to 1.16) at four to six weeks as compared to other interventions. Only one RCT reported data for long-term changes, which found that the group that received intense pulse light as the treatment had complete eradication of Demodex mites at three months. We graded the certainty of the evidence for this outcome as very low. Three RCTs reported no evidence of a difference for participant reported symptoms measured on the Ocular Surface Disease Index (OSDI) between the tea tree oil group and the group receiving other forms of intervention. Mean differences in these studies ranged from -10.54 (95% CI - 24.19, 3.11) to 3.40 (95% CI -0.70 7.50). We did not conduct a meta-analysis for this outcome given substantial statistical heterogeneity and graded the certainty of the evidence as low. One RCT provided information concerning visual acuity but did not provide sufficient data for between-group comparisons. The authors noted that mean habitual LogMAR visual acuity for all study participants improved post-treatment (mean LogMAR 1.16, standard deviation 0.26 at 4 weeks). We graded the certainty of evidence for this outcome as low. No RCTs provided data on mean change in number of cylindrical dandruff or the proportion of participants experiencing conjunctival injection or experiencing meibomian gland dysfunction. Three RCTs provided information on adverse events. One reported no adverse events. The other two described a total of six participants randomized to treatment with tea tree oil who experienced ocular irritation or discomfort that resolved with re-educating the patient on application techniques and continuing use of the tea tree oil. We graded the certainty of the evidence for this outcome as very low. AUTHORS' CONCLUSIONS: The current review suggests that there is uncertainty related to the effectiveness of 5% to 50% tea tree oil for the short-term treatment of Demodex blepharitis; however, if used, lower concentrations may be preferable in the eye care arena to avoid induced ocular irritation. Future studies should be better controlled, assess outcomes at long term (e.g. 10 to 12 weeks or beyond), account for patient compliance, and study the effects of different tea tree oil concentrations.

Adjudication rather than experience of data abstraction matters more in reducing errors in abstracting data in systematic reviews.

BACKGROUND: During systematic reviews, "data abstraction" refers to the process of collecting data from reports of studies. The data abstractors' level of experience may affect the accuracy of data abstracted. Using data from a randomized crossover trial in which different data abstraction approaches were compared, we examined the association between abstractors' level of experience and accuracy of data abstraction. METHODS: We classified abstractors as "more experienced" if they had authored three or more published systematic reviews, and "less experienced" otherwise. Each abstractor abstracted data related to study design, baseline characteristics, and outcomes/results from six articles. We considered two types of errors: incorrect abstraction and errors of omission. We estimated the proportion of errors by level of experience using a binomial generalized linear mixed model. RESULTS: We used data from 25 less experienced and 25 more experienced data abstractors. Overall error proportions were similar for less experienced abstractors (21%) and more experienced abstractors (19%). Compared with less experienced abstractors, more experienced abstractors had a lower odds of errors for data items related to outcomes/results (adjusted odds ratio [OR] = 0.53; 95% CI, 0.34-0.82) and potentially for data items related to study design (adjusted OR = 0.83; 95% CI, 0.64-1.09) but a potentially higher odds of errors for items related to baseline characteristics (adjusted OR = 1.42; 95% CI, 0.97-2.06). CONCLUSION: Experience of data abstraction matters little. Errors are reduced by adjudication but still remain high for data items related to outcomes/results.

Patient-reported outcomes measures and patient preferences for minimally invasive glaucoma surgical devices.

BACKGROUND: Many therapeutic options are available to glaucoma patients. One recent therapeutic option is minimally invasive glaucoma surgical (MIGS) devices. It is unclear how patients view different treatments and which patient-reported outcomes would be most relevant in patients with mild to moderate glaucoma. We developed a questionnaire for patients eligible for MIGS devices and a patient preference study to examine the value patients place on certain outcomes associated with glaucoma and its therapies. OBJECTIVES: To summarize the progress to date. METHODS: Questionnaire development: We drafted the questionnaire items based on input from one physician and four patient focus groups, and a review of the literature. We tested item clarity with six cognitive interviews. These items were further refined. Patient preference study: We identified important benefit and risk outcomes qualitatively using semi-structured, one-on-one interviews with patients who were eligible for MIGS devices. We then prioritized these outcomes quantitatively using best-worst scaling methods. RESULTS: Questionnaire testing: Three concepts were deemed relevant for the questionnaire: functional limitations, symptoms, and psychosocial factors. We will evaluate the reliability and validity of the 52-item draft questionnaire in an upcoming field test. Patient preference study: We identified 13 outcomes that participants perceived as important. Outcomes with the largest relative importance weights were "adequate IOP control" and "drive a car during the day." CONCLUSIONS: Patients have the potential to steer clinical research towards outcomes that are important to them. Incorporating patients' perspectives into the MIGS device development and evaluation process may expedite innovation and availability of these devices.

Evaluation of Systematic Reviews of Interventions for Retina and Vitreous Conditions.

Importance: Patient care and clinical practice guidelines should be informed by evidence from reliable systematic reviews. The reliability of systematic reviews related to forthcoming guidelines for retina and vitreous conditions is unknown. Objectives: To summarize the reliability of systematic reviews on interventions for 7 retina and vitreous conditions, describe characteristics of reliable and unreliable systematic reviews, and examine the primary area in which they appeared to be lacking. Design, Setting, and Participants: A cross-sectional study of systematic reviews was conducted. Systematic reviews of interventions for retina- and vitreous-related conditions in a database maintained by the Cochrane Eyes and Vision United States Satellite were identified. Databases that the reviewers searched, whether any date or language restrictions were applied, and bibliographic information, such as year and journal of publication, were documented. The initial search was conducted in March 2007, and the final update was performed in July 2018. The conditions of interest were age-related macular degeneration; diabetic retinopathy; idiopathic epiretinal membrane and vitreomacular traction; idiopathic macular hole; posterior vitreous detachment, retinal breaks, and lattice degeneration; retinal and ophthalmic artery occlusions; and retinal vein occlusions. The reliability of each review was evaluated using prespecified criteria. Data were extracted by 2 research assistants working independently, with disagreements resolved through discussion or by 1 research assistant with verification by a senior team member. Main Outcomes and Measures: Proportion of reviews that meet all of the following criteria: (1) defined eligibility criteria for study selection, (2) described conducting a comprehensive literature search, (3) reported assessing risk of bias in included studies, (4) described using appropriate methods for any meta-analysis performed, and (5) provided conclusions consistent with review findings. Results: A total of 327 systematic reviews that addressed retina and vitreous conditions were identified; of these, 131 reviews (40.1%) were classified as reliable and 196 reviews (59.9%) were classified as not reliable. At least 1 reliable review was found for each of the 7 retina and vitreous conditions. The most common reason that a review was classified as not reliable was lack of evidence that a comprehensive literature search for relevant studies had been conducted (149 of 196 reviews [76.0%]). Conclusion and Relevance: The findings of this study suggest that most systematic reviews that addressed interventions for retina and vitreous conditions were not reliable. Systematic review teams and guideline developers should work with information professionals who can help navigate sophisticated and varied syntaxes required to search different resources.

Outcome Specification in a Sample of Publicly Funded Eye and Vision Trials Registered on ClinicalTrials.gov.

IMPORTANCE: For findings from clinical trials to be actionable, outcomes measured in trials must be fully defined and, when appropriate, defined consistently across trials. Otherwise, it is difficult to compare findings between trials, combine results in meta-analyses, or leverage findings collectively to inform health care decision-making. OBJECTIVE: To identify and characterize outcomes specified in ClinicalTrials.gov records for publicly funded clinical trials for 3 high-burden, high-prevalence eye conditions. DESIGN, SETTING, AND PARTICIPANTS: ClinicalTrials.gov, a registry of publicly and privately supported clinical studies, was searched on January 31, 2019, for records of clinical trials for age-related macular degeneration (AMD), dry eye, or refractive error. The search was limited to trials funded by the National Eye Institute but did not impose a date restriction. Five elements of a well-specified outcome were extracted from each outcome stated in each record, including the domain, method of measurement, metric, method of aggregation, and time points. MAIN OUTCOMES AND MEASURES: Number of outcome domains specified for trials for AMD, dry eye, and refractive error and the number of trial records specifying each unique domain. RESULTS: A total of 49 unique outcome domains specified across 39 records of trials were identified. The median (interquartile range) number of records specifying each unique outcome domain was 1 (1-3), 1.5 (1-2), and 1 (1-1) for AMD, dry eye, and refractive error, respectively. Even when the same domains were registered across multiple trials, the time point, specific metric, and method of aggregation were specified in multiple ways. CONCLUSIONS AND RELEVANCE: There were too many outcomes with too little overlap in the sample of trials that were examined. Differences in how outcomes are measured across trials make it difficult to compare results, even for well-established domains, such as visual acuity. To reduce this waste in eye and vision research, the time is ripe for agreeing on what outcomes to measure.

Assessing progress of the Pan American Health Organization's Policy Research for Health in member states / Evaluación del progreso de la Política sobre Investigación Sanitaria de la Organización Panamericana de la Salud en sus Estados miembros

The improvement of health in the twenty-first century is inextricably linked to research for health. In response to growing international appeal to address regional health needs, the Pan American Health Organization (PAHO) and its Member States approved the Policy on Research for Health (CD49/10) in 2009. This document represents the flagship regional policy on research for health and outlines how health systems and services in the region can be strengthened through research. It has been implemented by the two components of PAHO -the Member States and the Pan American Sanitary Bureau. The policy contained a specific directive mandating PAHO to report on its implementation, development of subsequent strategies, and action plans targeting its governing bodies. The Americas are the first World Health Organization (WHO) region to issue a regional Policy on Research for Health, which was harmonized with WHO's Strategy on Research for Health, approved in 2010. Attending to the recommendations issued by PAHO's Advisory Committee on Health Research and WHO's Advisory Committee on Health Research, the PAHO Department of Knowledge Management, Bioethics and Research set out to advance the assessment of the implementation of the Policy on Research for Health through the creation of a monitoring and evaluation Scorecard. Indicators relevant to the Policy on Research for Health objectives were mapped from the Compendium of Impact and Outcome Indicators, with new indicators created. A practical framework based on available indicator data was proposed to generate a baseline policy assessment and incorporate a means of incrementally enhancing the measurements. In this case study, we outline the iterations of the PAHO Policy on Research for Health Scorecard, as well as the lessons learned throughout the development process that may be a valuable guide for health research entities monitoring and evaluating the progress of their own policies

La mejora de la salud en el siglo XXI está inextricablemente ligada a la investigación sanitaria. En respuesta a la llamada internacional creciente, de cara a abordar las necesidades sanitarias regionales, la Organización Panamericana de la Salud (OPS) y sus Estados miembros aprobaron en 2009 la Política sobre Investigación Sanitaria (CD49/10). Este documento constituye la política regional insignia sobre investigación sanitaria, y destaca cómo pueden reforzarse los sistemas y servicios sanitarios en la región a través de la investigación. Ha sido implementado por parte de los dos componentes de la OPS: los Estados miembros y la Agencia Sanitaria Panamericana. La política contenía una directiva específica, que encomendaba a la OPS la realización de un informe sobre su implementación, desarrollo y políticas subsiguientes, al igual que los planes de acción dirigidos a sus órganos directivos. El continente americano es la primera región de la Organización Mundial de la Salud (OMS) que establece una política regional sobre investigación sanitaria, armonizada con la Estrategia sobre investigación sanitaria de la OMS, aprobada en 2010. Atendiendo a las recomendaciones emitidas por el Comité Asesor sobre investigación sanitaria de la OPS y el Comité Asesor sobre investigación sanitaria de la OMS, el Departamento de Gestión del Conocimiento, Bioética e Investigación de la OPS propuso avanzar en la evaluación de la implementación de la política de investigación sanitaria a través de la creación de un cuadro de mando de supervisión y evaluación. Los indicadores relevantes de los objetivos de la política sobre investigación sanitaria fueron pareados a partir de los indicadores de Compendio del Impacto y Resultados, con los nuevos indicadores. Se propuso un marco práctico basado en los datos indicadores disponibles, para generar una evaluación de la política basal e incorporar un medio de mejorar las medidas gradualmente. En este estudio de caso destacamos las iteraciones del cuadro de mando de la política sobre investigación sanitaria de la OPS, así como las lecciones aprendidas a lo largo del proceso de desarrollo, que podrían constituir una guía valiosa para las entidades de investigación sanitaria de cara a supervisar y evaluar el progreso de sus propias políticas