Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration.

Purpose: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods: Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

The association between perceived cause of glaucoma and illness perceptions.

Purpose: The perceived cause of disease is an important factor that has been linked with treatment outcomes but has not been fully assessed in primary open-angle glaucoma (POAG). This study assessed the accuracy of patients' perceived cause of POAG and identified associations between accuracy, illness perceptions, medication adherence, and quality of life (QoL). Methods: The Brief Illness Perception Questionnaire (BIPQ) was used to assess illness perceptions and asked patients to rank the three most important causes of their disease in order of importance. POAG risk factors recognized by the American Academy of Ophthalmology were used to code responses as accurate or inaccurate based on the following three methods: (1) coding any reported cause, regardless of rank, (2) coding only the first-ranked cause, and (3) coding and weighting all reported causes. Medication adherence was measured electronically. QoL was measured using the Glaucoma Quality of Life questionnaire. Mann-Whitney U test was used to detect differences in illness perceptions, medication adherence, and QoL between accuracy groups. Results: A total of 97 patients identified a cause of their POAG and were included in this analysis. A higher proportion of patients reported an accurate cause (86.6% using method 1, 78.4% using method 2, and 79.4% using method 3; all p < 0.001). Mean medication adherence was 86.0% ± 17.8 and was similar across accuracy groups (all p > 0.05). Using method 2 (p = 0.045) and method 3 (p = 0.028), patients who reported an accurate cause of their POAG believed that their illness would last for a longer time compared to patients who reported an inaccurate cause. Method 3 also revealed that patients who reported an accurate cause of their POAG had lower perceived understanding of their illness (p = 0.048) compared to patients who reported an inaccurate cause. There were no differences in QoL between accuracy groups (all p > 0.05). Conclusion: This study highlights the association between perceived cause of POAG and illness perceptions related to knowledge level and POAG duration. Future studies should assess associations between perceived cause of disease and other critical dimensions of illness perception.

Protecting Abortion with State Health Care Freedom of Choice.

This essay examines the right of health care freedom of choice contained in some state constitutions. It explores how courts have, and could, use this constitutional health care right as a basis for recognizing or reinforcing a fundamental right to choose an abortion.

Incidence of CD19-negative relapse after CD19-targeted immunotherapy in R/R BCP acute lymphoblastic leukemia: a review.

There are inconsistencies in the reporting of CD19 antigen status following treatment with CD19-targeted therapies. A majority of evidence comes from studies reporting small sample sizes. In this review, we systematically summarize published studies that have reported rates of CD19-negative relapse after treatment with either blinatumomab or CD19-directed CAR T-cell therapy and report the rates of CD19-negative relapse when evaluated in a standardized way across trials. CD19-negative relapse appears to occur more commonly in relapses following CAR T-cell therapy compared with blinatumomab, whether proportions are calculated among all treated patients (8.7% vs 4.5%) or among patients who relapse (30% vs 22.5%). The median (range) duration of follow-up was 29.3 (17.4-50.8) and 20.4 (6.9-49.0) months for publications on blinatumomab (n = 10) and CAR T-cell therapies (n = 23), respectively. There is a need for standardized reporting of CD19 antigen status in the setting of relapse following novel immunotherapies to inform clinical practice.

Global Epidemiology of Hip Fractures: Secular Trends in Incidence Rate, Post-Fracture Treatment, and All-Cause Mortality.

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Conceptual Framework for Understanding Incident Management Systems During Public Health Emergencies.

OBJECTIVE: Effective incident management is essential for coordinating efforts of multiple disciplines and stakeholders when responding to emergencies, including public health disasters such as the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: Existing research frameworks tend to focus on formal structures and doctrine (eg, ICS-NIMS); however, organizational processes that underlie incident management have not been systematically assessed and synthesized into a coherent conceptual framework. RESULTS: The lack of a framework has hindered the development of measures of performance that could be used to further develop the evidence base and facilitate process improvement. To address this gap, we present a conceptual framework of incident management drawn from expert feedback and a review of literature on incident management and related fields. The framework features 23 measurement constructs grouped into 5 domains: (1) situational awareness and information sharing, (2) incident action and implementation planning, (3) resource management and mobilization, (4) coordination and collaboration, and (5) feedback and continuous quality improvement. CONCLUSIONS: As such, the article provides a first step toward the development of robust measures for assessing the performance and effectiveness of incident management systems.

The Impact of the Coronavirus Disease 2019 Pandemic on Adherence to Ocular Hypotensive Medication in Patients with Primary Open-Angle Glaucoma.

PURPOSE: Emerging evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic is disrupting health behaviors such as medication adherence. The objective of this study was to determine whether adherence to ocular hypotensive medication was affected by the pandemic and to identify factors associated with this change. DESIGN: In this cohort study, we used a controlled interrupted time series design in which the interruption was the declaration of the COVID-19 pandemic in the United States on March 13, 2020. The 300-day monitoring period, which evenly bracketed this declaration, started on October 16, 2019, and ended on August 10, 2020. PARTICIPANTS: Patients with primary open-angle glaucoma enrolled in an ongoing longitudinal National Institutes of Health-funded study initiated before the onset of the pandemic were selected if they were prescribed ocular hypotensive medication and had adherence data spanning the 300-day period. METHODS: We applied segmented regression analysis using a "slope change following a lag" impact model to obtain the adherence slopes in the periods before and after the segmentation. We compared the 2 slopes using the Davies test. MAIN OUTCOME MEASURES: The main outcome measure was daily adherence to ocular hypotensive medication, defined as the number of doses taken divided by the number of doses prescribed, expressed in percent. Adherence was measured objectively using Medication Event Monitoring System caps. We assessed the associations between change in adherence and demographic, clinical, and psychosocial factors. RESULTS: The sample included 79 patients (mean age, 71 years [standard deviation, 8 years]). Segmented regression identified a breakpoint at day 28 after the declaration of the pandemic. The slope in the period after the breakpoint (-0.04%/day) was significantly different from zero (P < 0.001) and from the slope in the period before the breakpoint (0.006%/day; P < 0.001). Mean adherence in the period before the segmentation breakpoint was significantly worse in Black patients (median, IQR: 80.6%, 36.2%) compared with White patients (median, IQR: 97.2%, 8.7%; chi-square, 15.4; P = 0.0004). A significant positive association was observed between the Connor-Davidson resilience score and the change in slope between the periods before and after the breakpoint (P = 0.002). CONCLUSIONS: Adherence to ocular hypotensive medication worsened during the COVID-19 pandemic and seems to be related to patient resilience. This collateral consequence of the pandemic may translate into vision loss that may manifest beyond its containment.

Overview of the Translation, Dissemination, and Implementation of Public Health Preparedness and Response Research and Training Initiative.

We provide an overview of a Centers for Disease Control and Prevention-funded public health preparedness and response (PHPR) research and training initiative to improve public health practice. Our objectives were to accelerate the translation, dissemination, and implementation (TDI) of promising PHPR evidence-based tools and trainings developed by the Preparedness and Emergency Response Research Centers (PERRC) or the Preparedness and Emergency Response Learning Centers (PERLC) between 2008 and 2015. Nine competitive awards were made to seven academic centers to achieve predetermined TDI objectives. The outputs attained by the initiative included: user-friendly online repositories of PERRC and PERLC tools and trainings; training courses that addressed topics; a community resilience manual to synthesize, translate, and implement evidence-based programs; and Web applications that supported legal preparedness, exercise evaluation, and immunization education. The evaluation identified several best practices and potential barriers to implementation. As illustrated by the work in this supplement, the broader awareness and implementation of PERRC preparedness products and PERLC trainings and the continued evaluation of their impact could enhance the PHPR capacity and capability of the nation, which could lead to improved health security.

Applying Instructional Design Strategies and Behavior Theory to Household Disaster Preparedness Training.

CONTEXT: Interventions and media campaigns promoting household disaster preparedness have produced mixed results in affecting behaviors. In large part, this is due to the limited application of instructional design strategies and behavior theory, such as the Transtheoretical Model (TTM). This study describes the development and evaluation of Ready CDC, an intervention designed to increase household disaster preparedness among the Centers for Disease Control and Prevention (CDC) workforce. OBJECTIVES: (1) Describe the instructional design strategies employed in the development of Ready CDC and (2) evaluate the intervention's impact on behavior change and factors influencing stage progression for household disaster preparedness behavior. DESIGN: Ready CDC was adapted from the Federal Emergency Management Agency's (FEMA's) Ready campaign. Offered to CDC staff September 2013-November 2015, it consisted of a preassessment of preparedness attitudes and behaviors, an in-person training, behavioral reinforcement communications, and a 3-month follow-up postassessment. RESULTS: Ready CDC employed well-accepted design strategies, including presenting stimulus material and enhancing transfer of desired behavior. Excluding those in the TTM "maintenance" stage at baseline, this study determined 44% of 208 participants progressed at least 1 stage for developing a written disaster plan. Moreover, assessment of progression by stage found among participants in the "precontemplation" (n = 16), "contemplation" (n = 15), and "preparation" (n = 125) stages at baseline for assembling an emergency kit, 25%, 27%, and 43% moved beyond the "preparation" stage, respectively. Factors influencing stage movement included knowledge, attitudes, and community resiliency but varied depending on baseline stage of change. CONCLUSIONS: Employing instructional strategies and behavioral theories in preparedness interventions optimizes the potential for individuals to adopt preparedness behaviors. Study findings suggest that stage movement toward household preparedness was not spurious but rather associated with the intervention. Therefore, Ready CDC was successful in moving staff along the continuous process of adopting household disaster preparedness behaviors, thus providing a model for future interventions. The TTM suggests factors such as knowledge, beliefs, and self-efficacy will differ by stage and may differentially predict progression towards behavior adoption. Thus, tailoring interventions based on an individual's stage of change optimizes the potential for individuals to adopt desired behaviors.

Proposing a Framework for Mobile Applications in Disaster Health Learning.

Mobile applications, or apps, have gained widespread use with the advent of modern smartphone technologies. Previous research has been conducted in the use of mobile devices for learning. However, there is decidedly less research into the use of mobile apps for health learning (eg, patient self-monitoring, medical student learning). This deficiency in research on using apps in a learning context is especially severe in the disaster health field. The objectives of this article were to provide an overview of the current state of disaster health apps being used for learning, to situate the use of apps in a health learning context, and to adapt a learning framework for the use of mobile apps in the disaster health field. A systematic literature review was conducted by using the PRISMA checklist, and peer-reviewed articles found through the PubMed and CINAHL databases were examined. This resulted in 107 nonduplicative articles, which underwent a 3-phase review, culminating in a final selection of 17 articles. While several learning models were identified, none were sufficient as an app learning framework for the field. Therefore, we propose a learning framework to inform the use of mobile apps in disaster health learning. (Disaster Med Public Health Preparedness. 2017;11:487-495).

Influences of Preparedness Knowledge and Beliefs on Household Disaster Preparedness.

In response to concern about strengthening the nation's ability to protect its population and way of life (i.e., security) and ability to adapt and recover from emergencies (i.e., resilience), the President of the United States issued Presidential Policy Directive 8: National Preparedness (PPD-8) (1). Signed on March 30, 2011, PPD-8 is a directive for the U.S. Department of Homeland Security to coordinate a comprehensive campaign across government, private and nonprofit sectors, and individuals to build and sustain national preparedness. Despite efforts by the Federal Emergency Management Agency (FEMA) and other organizations to educate U.S. residents on becoming prepared, growth in specific preparedness behaviors, including actions taken in advance of a disaster to be better prepared to respond to and recover, has been limited (2). In 2012, only 52% of U.S. residents surveyed by FEMA reported having supplies for a disaster (2), a decline from 57% who reported having such supplies in 2009 (3). It is believed that knowledge influences behavior, and that attitudes and beliefs, which are correlated with knowledge, might also influence behavior (4). To determine the association between knowledge and beliefs and household preparedness, CDC analyzed baseline data from Ready CDC, a personal disaster preparedness intervention piloted among Atlanta- and Morgantown-based CDC staff members during 2013­2015. Compared with persons with basic preparedness knowledge, persons with advanced knowledge were more likely to have assembled an emergency kit (44% versus 17%), developed a written household disaster plan (9% versus 4%), and received county emergency alert notifications (63% versus 41%). Similarly, differences in household preparedness behaviors were correlated with beliefs about preparedness. Persons identified as having strong beliefs in the effectiveness of disaster preparedness engaged in preparedness behaviors at levels 7%­30% higher than those with weaker preparedness beliefs. Understanding the influences of knowledge and beliefs on household disaster preparedness might provide an opportunity to inform messages promoting household preparedness.

Assessing immunization interventions in the Women, Infants, and Children (WIC) program.

BACKGROUND: Vaccination promotion strategies are recommended in Women, Infants, and Children (WIC) settings for eligible children at risk for under-immunization due to their low-income status. PURPOSE: To determine coverage levels of WIC and non-WIC participants and assess effectiveness of immunization intervention strategies. METHODS: The 2007-2011 National Immunization Surveys were used to analyze vaccination histories and WIC participation among children aged 24-35 months. Grantee data on immunization activities in WIC settings were collected from the 2010 WIC Linkage Annual Report Survey. Coverage by WIC eligibility and participation status and grantee-specific coverage by intervention strategy were determined at 24 months for select antigens. Data were collected 2007-2011 and analyzed in 2013. RESULTS: Of 13,183 age-eligible children, 5,699 (61%, weighted) had participated in WIC, of which 3,404 (62%, weighted) were current participants. In 2011, differences in four or more doses of the diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccine by WIC participation status were observed: 86% (ineligible); 84% (current); 77% (previous); and 69% (never-eligible). Children in WIC exposed to an immunization intervention strategy had higher coverage levels than WIC-eligible children who never participated, with differences as great as 15% (DTaP). CONCLUSIONS: Children who never participated in WIC, but were eligible, had the lowest vaccination coverage. Current WIC participants had vaccination coverage comparable to more affluent children, and higher coverage than previous WIC participants.

Predictors of incident heart failure in a large insured population: a one million person-year follow-up study.

BACKGROUND: Studies on the incidence and predictors of heart failure (HF) are often restricted to elderly persons or identify only inpatient cases. METHODS AND RESULTS: We determined the incidence and predictors of new HF diagnosed in either outpatient or inpatient settings, among 359 947 women and men (age ≥18 years) insured by Kaiser Permanente Georgia at any time during calendar years 2000 to 2005. Subjects were free of HF at baseline, and incident HF was identified with ICD-9 codes (1 inpatient or 2 outpatient HF visits). We developed multivariable Cox models to assess the association of antecedent factors (coronary heart disease, hypertension, diabetes mellitus, atrial fibrillation, and valvular heart disease) with incident HF. Separate models were created for each sex and for newly diagnosed HF in outpatient or inpatient settings. There were 4001 incident HF cases (50% women and 48% in subjects <65 years old), during 1 015 794 person-years of follow-up. The incidence rate of HF was greater in men than in women (4.24 versus 3.68 per 1000 person-years) but was stable across the study interval in both sexes. Two thirds of incident HF cases from this population occurred in outpatients. These 5 antecedent factors and age yielded excellent discrimination for incident HF in both outpatients and inpatients and in both sexes (C >0.85 in all models). CONCLUSIONS: Common modifiable risk factors accurately discriminate women and men at risk for HF diagnosed in either outpatient or inpatient settings. Approximately two thirds of new HF cases in our insured population were diagnosed in outpatients; more research is needed to characterize these subjects and their prognosis.

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol.

BACKGROUND: Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. METHODS: Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study. RESULTS: Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p < 0.05). Mean plasma concentrations of both drugs were higher, earlier, following administration of the combination tablet compared with monotherapy. Mean plasma levels at 10 and 20 minutes were 6.64 microg x mL(-1) and 16.81 microg x mL(-1), respectively, for ibuprofen from the combination, compared with 0.58 microg x mL(-1) and 9.00 microg x mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 microg x mL(-1) and 14.54 microg x mL(-, respectively, for the combination compared with 0.33 microg x mL(-1) and 9.19 microg x mL(-1), respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p < 0.001). The pharmacokinetic parameters were comparable irrespective of whether the combination tablet was given twice or three times daily; systemic exposure was, however, approximately 1.4 times greater for both drugs when given three times daily. CONCLUSIONS: Administration of ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug, except for enhancing the rate of paracetamol absorption, offering potential therapeutic benefits in relation to the onset of analgesia. Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state. Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing.

Woolly hair nevus with an ipsilateral associated epidermal nevus and additional findings of a white sponge nevus.

We report a case of a 16-year-old male with a woolly hair nevus, an associated ipsilateral epidermal nevus who also had a white plaque on his tongue, clinically diagnosed as a white sponge nevus. The concurrent findings of a white sponge nevus, a woolly hair nevus, and an ipsilateral epidermal nevus, to our knowledge, have not been previously reported.

Vicious dogs: the antisocial behaviors and psychological characteristics of owners.

Each year, 4.7 million people are bitten by dogs. Of those bitten each year, 386,000 are seriously injured and some killed. Consequently, many insurance companies refuse to issue homeowners insurance to owners of specific breeds of dogs considered "vicious" or high risk of causing injury. This study examined whether vicious dog owners were different on antisocial behaviors and personality dimensions. A total of 869 college students completed an anonymous online questionnaire assessing type of dog owned, criminal behaviors, attitudes towards animal abuse, psychopathy, and personality. The sample was divided into four groups: vicious dog owners, large dog owners, small dog owners, and controls. Findings revealed vicious dog owners reported significantly more criminal behaviors than other dog owners. Vicious dog owners were higher in sensation seeking and primary psychopathy. Study results suggest that vicious dog ownership may be a simple marker of broader social deviance.

A review of the smallpox vaccine adverse events active surveillance system.

In response to concern about smallpox possibly being used as a biological weapon, the President of the United States launched the National Smallpox Pre-Event Vaccination Program on 13 December 2002. Given safety concerns, identifying potentially serious adverse events (SAEs) was an essential tool of the program. To monitor for SAEs, both enhanced passive surveillance and active surveillance systems were used. The enhanced passive system was built, in part, on the existing Vaccine Adverse Event Reporting System; the active system was implemented 24 January 2003. During January 2003-May 2005, the active system detected only 1 SAE in addition to those reported through the enhanced passive system. Furthermore, the active system was not universally used by states. With the enhancements to passive surveillance, the performance of enhanced passive surveillance was comparable to that of active surveillance. However, an active surveillance system may be important when there is no enhanced passive surveillance system available.

Expression of vascular endothelial growth factor in early cutaneous melanocytic lesion progression.

BACKGROUND: A considerable body of evidence supports the concept that a significant number of cutaneous malignant melanomas progress through a precursor lesion or dysplastic melanocytic nevi (DN). Tumor angiogenesis likely plays a critical role in early development of melanoma, and intermediate biomarkers of angiogenesis could be useful as chemoprevention and prognostic markers. METHODS: Markers of angiogenesis that included expression of the vascular endothelial growth factor A (VEGF-A) and microvessel density counts (MVD) were evaluated in 13 prospectively collected benign nevi (BN) and 19 DN from 16 individuals and in a comparison group of 17 primary melanomas (16 archival samples and 1 prospective melanoma). RESULTS: VEGF expression in melanocytic cells (mean+/-standard error [SE]) was low or absent in BN (3.4+/-1.4), increased significantly in DN (41.0+/-10.1; P=.0003 for BN vs DN), and increased further in primary melanoma (119.9+/-28.3; P = .06 for DN vs melanoma). MVD using CD31 (mean+/-SE [percentage x intensity]) followed a similar pattern with similarity between BN (2.6+/-0.7; N=13) and DN (2.2+/-0.8; N=19; P=.4 for BN vs DN), whereas primary melanomas were significantly higher (39.4+/-6.4; N=17; P=.0001 for BN or DN vs melanoma). CONCLUSIONS: In a prospective setting, the current data suggested that increased VEGF-A expression in DN may be a good indicator of preneoplastic change in melanocytic lesions with the potential for improving the understanding and prevention of the transformation of DN to melanoma.