Characteristics of Prescreened Patients Who Did Not Participate in the Zoster Eye Disease Study.

PURPOSE: The Zoster Eye Disease Study (ZEDS) is a multicenter randomized clinical trial (RCT) funded by the National Eye Institute aiming to determine the efficacy of suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) that enrolled fewer participants than planned (527/780, 67.6%). Understanding reasons for nonparticipation of likely eligible prescreened patients provides insights into patient populations that are not represented by ZEDS and barriers in clinical trials. METHODS: In this retrospective cohort study, HZO adults likely eligible for ZEDS with a history of a typical rash and a medical record within the past year of an episode of epithelial or stromal keratitis or iritis were prescreened at activated Participating Clinical Centers from 2017 to 2022 using a standard prescreening log. De-identified data including demographic information, reasons for exclusion because of ineligibility, and patient refusal were retrospectively entered into REDCap and analyzed. RESULTS: Prescreening logs with reasons for nonconsent (1244/1706, 72.9%) were included in the data set. Patients were excluded from the study (915/1244, 73.6%) because they did not meet all inclusion criteria (619/915, 67.7%) or met an exclusion criterion (296/915, 32.3%). Among the 12 exclusion criteria for the ZEDS study, immunocompromise (76/296, 25.7%) and renal insufficiency (50/296, 16.9%) were most frequently reported. Patient refusal to participate (327/1,244, 26.3%) was common. CONCLUSION: The most common reasons for ineligibility were immunocompromise and renal insufficiency. There may be benefits to long-term antiviral use in these populations not captured in ZEDS. A quarter (26.3%) of prescreened patients refused participation, showing the substantial impact of patient preferences on trial participation.

Baseline Participant Characteristics at Enrollment in the Zoster Eye Disease Study.

PURPOSE: The Zoster Eye Disease Study (ZEDS) is the first randomized clinical trial to study the efficacy of long-term (1 year) suppressive valacyclovir treatment on herpes zoster ophthalmicus (HZO) outcomes. This article details the baseline characteristics of participants. SETTING: The study was set at 95 participating clinical centers in 33 states, Canada, and New Zealand. STUDY POPULATION: Immunocompetent adults with a history of a characteristic HZO unilateral rash and documentation of an episode of active dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, or iritis within the preceding year, enrolled in ZEDS from November 2017 to January 2023. INTERVENTION: Participants were randomized to double-masked oral valacyclovir 1 gm daily versus placebo for 1 year of treatment and followed for 18 months. RESULTS: Five hundred twenty-seven participants were enrolled across 4 strata according to age at HZO onset (younger or older than 60 years) and duration of HZO at enrollment (less or greater than 6 months), with an even distribution of men and women and a median age of 60 years. More participants with recent (57%, 300/527) than chronic HZO and younger than 60 years at HZO onset (54%, 286/527) were enrolled. Most participants were treated acutely with a recommended antiviral regimen (91%, 480/527) and had not been vaccinated against zoster (79%, 418/527). CONCLUSIONS: The broad ZEDS study population enhances the likelihood that ZEDS will provide generalizable high-quality evidence regarding the efficacy and safety of suppressive valacyclovir for HZO immunocompetent adults and whether it should become standard of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03134196.

Which first-line treatment for cutaneous sarcoidosis? A retrospective study of 120 patients.

Sarcoidosis is a systemic disease that affects the skin in about 25% of patients. The treatment of cutaneous sarcoidosis is guided by the extent of lesions, associated symptoms and organ involvement. To evaluate rates of response to various potential first-line treatments for cutaneous sarcoidosis during the year following treatment initiation. This retrospective multicentre study included 120 patients with cutaneous sarcoidosis. Treatment response was assessed retrospectively from the patients' medical records. Univariate logistic regression analysis, with an estimation of unadjusted odds ratios (OR) and their 95% CI ,was performed to identify factors associated with complete cutaneous remission (CR), followed by multivariate logistic regression analysis. At one year, 43 of the 120 (36%) included patients had CR. The best response rates were obtained with oral corticosteroids (12/21, 57%), followed by a combination of hydroxychloroquine and topical steroids (6/13, 46%). In multivariate analysis, lupus pernio was the only predictor of a poor cutaneous response. We suggest the use of a combination of hydroxychloroquine and topical steroids as an optimal first-line treatment for cutaneous sarcoidosis, given the known adverse effects of systemic corticosteroids.

Apparent lack of association of COVID-19 vaccination with Herpes Zoster.

Purpose: Herpes zoster (HZ) has been identified as a potential association with the BNT162b2 COVID-19 vaccination. This study evaluated this possible association in a cohort of patients receiving the vaccination. Methods: Epic electronic health records of adult patients who received at least one COVID-19 vaccination between January 12, 2020 and 9/30/2021 within the NYU Langone Health were reviewed to analyze a new diagnosis of herpes zoster within 3 months before compared to 3 months after vaccination. Results: Of the 596,111 patients who received at least one COVID-19 vaccination, 716 patients were diagnosed with HZ within three months prior to vaccination, compared to 781 patients diagnosed within 3 months afterwards. Using the chi-square test for independence of proportions, there was not a statistically significant difference in frequency of HZ before (proportion: 0.0012, 95% CI: [0.0011, 0.0013]) vs. after vaccination (proportion: 0.0013, 95% CI: [0.0012, 0.0014]); (p = 0.093). Conclusions and importance: This study did not find evidence of an association between COVID-19 vaccination and a new diagnosis of HZ. We encourage health care professionals to strongly recommend COVID-19 vaccinations per Centers for Disease Control (CDC) recommendations and vaccination against HZ according to Food and Drug Administration (FDA) approval for the recombinant zoster vaccine.

A Preliminary Evaluation of Students' Learning and Performance Outcomes in an Accelerated 3-Year MD Pathway Program.

BACKGROUND: Little outcome data exist on 3-year MD (3YMD) programs to guide residency program directors (PDs) in deciding whether to select these graduates for their programs. OBJECTIVE: To compare performance outcomes of 3YMD and 4-year MD (4YMD) students at New York University Grossman School of Medicine. METHODS: In 2020, using the Kirkpatrick 4-level evaluation model, outcomes from 3 graduating cohorts of 3YMD students (2016-2018) were compared with the 4YMD counterparts. RESULTS: Descriptive statistics compared outcomes among consented student cohorts: 92% (49 of 53) 3YMD, 87% (399 of 459) 4YMD-G, and 84% (367 of 437) 4YMD-S. Student survey response rates were 93% (14 of 15), 74% (14 of 19), and 89% (17 of 19) from 2016 to 2018. PDs' response rates were 58% (31 of 53, 3YMD) and 51% (225 of 441, 4YMD). Besides age, 3YMD and 4YMD cohorts did not differ significantly in admissions variables. Other than small statistically significant differences in the medicine shelf examination (3YMD mean 74.67, SD 7.81 vs 4YMD-G mean 78.18, SD 7.60; t test=3.02; P=.003) and USMLE Step 1 (3YMD mean 235.13, SD 17.61 vs 4YMD-S mean 241.70, SD 15.92; t test=2.644; P=.009 and vs 4YMD-G mean 242.39, SD 15.65; t test=2.97; P=.003) and Step 2 CK scores (3YMD mean 242.57, SD 15.58 vs 4YMD-S mean 248.55, SD 15.33; t test=2.55; P=.01 and vs 4YMD-G mean 247.83, SD 15.38; t test=2.97; P=.03), other metrics and overall intern ratings did not differ by pathway. CONCLUSIONS: Exploratory findings from a single institution suggest that 3YMD students performed similarly to 4YMD students in medical school and the first year of residency.

Zoster Eye Disease Study: Rationale and Design.

PURPOSE: The purpose of this study was to describe the rationale and design of the Zoster Eye Disease Study (ZEDS). METHODS: ZEDS is a National Eye Institute-supported randomized clinical trial designed to determine whether 1 year of suppressive valacyclovir in patients with herpes zoster ophthalmicus (HZO) reduces complications because there is currently no high-quality evidence to support its use. Eligible patients are 18 years and older, immunocompetent, have a history of a typical rash at disease onset, and have had a record of active epithelial or stromal keratitis or iritis within 1 year before enrollment. Exclusion criteria include estimated glomerular filtration rate less than 45 or pregnancy. The primary endpoint is the time to first occurrence of new or worsening dendriform epithelial keratitis, stromal keratitis without or with ulceration, endothelial keratitis, or iritis due to HZO during 12 months of study treatment requiring prespecified treatment changes. The study has 80% power to detect a 30% difference between treatment groups, with a 30% rate of endpoints by 1 year assumed among controls. Secondary and exploratory questions include whether there is a persistent treatment benefit during the 6 months after treatment, whether development of postherpetic neuralgia varies by treatment group, and whether vaccinations against herpes zoster affect study outcomes and coronavirus disease 19 status. RESULTS: Over approximately 4 years, over 400 study participants have been enrolled. CONCLUSIONS: ZEDS aims to provide scientific evidence on whether suppressive valacyclovir treatment improves outcomes in HZO and should become the standard of care.

Meeting the challenges of retention and enrollment of study participants in clinical trials during the COVID-19 pandemic from the study leadership perspective: Experience from the Zoster Eye Disease Study (ZEDS).

PURPOSE: To describe steps taken that enabled a high rate of retention and early resumption of enrollment in the Zoster Eye Disease Study (ZEDS), a randomized controlled trial funded by the National Eye Institute, during the first 13 months (3/1/2020-3/31/2021) of the COVID-19 pandemic. METHODS: A number of responses were implemented in ZEDS when the focus shifted to retention of study participants at the beginning of the pandemic including frequent communication with the participating clinical centers (PCCs) about remote visits, local lab work, shipping study medication, and completion of revised case report forms. Additional payments were provided to the PCCs. Remote activation of PCCs continued. Screening and enrollment visits gradually resumed when allowed. RESULTS: Communication with PCCs increased, and average attendance at monthly coordinator teleconferences went up from 17 to 47. Remote visits peaked in April 2020, accounting for 75% (33/44) of study visits, then declined to less than 10% of study visits beginning August 2020. Overall, 97% (590/609) of study visits were completed. Only 5.5% (9/165) of study participants withdrew consent, and 2.4% (4/165) were lost to follow-up. Enrollment returned to pre-pandemic levels by September 2020. DISCUSSION: Strong communication and unwavering commitment, combined with the technological capability for remote work, visits, and shipment of study medication, were key to the successful retention of study participants and resumption of enrollment. CONCLUSIONS: Rapid responses to challenges to trials caused by the COVID-19 pandemic can enable them to continue successfully and provide insights into the planning of future trials.

Herpes Zoster: A Brief Definitive Review.

ABSTRACT: This brief definitive review of herpes zoster (HZ) will cover the current state of knowledge and questions that remain to be answered regarding HZ in general and HZ ophthalmicus in particular. A question-and-answer format will be used to address various important topics related to this common and serious disease. Questions to be addressed relate to common misconceptions, contagiousness of infection, unknowns regarding pathogenesis, rising incidence, risk factors and complications, relationship with temporal arteritis, vaccination, and current and future antiviral treatment. In addition, the importance of the Zoster Eye Disease Study to determine the efficacy of suppressive valacyclovir treatment in preventing complications of HZ ophthalmicus and the need to support enrollment will be discussed.

Enrollment in the Zoster Eye Disease Study.

PURPOSE: To present the results of a survey of the Zoster Eye Disease Study (ZEDS) investigators regarding barriers to the enrollment of study participants and approaches to overcome them. METHODS: ZEDS is a multicenter randomized clinical trial supported by the National Eye Institute to determine whether prolonged suppressive valacyclovir reduces the complications of herpes zoster ophthalmicus (HZO), relative to placebo. Enrollment of study participants is currently far below expectations. An institutional review board-approved anonymous internet survey was conducted of ZEDS investigators to study their experiences and opinions regarding barriers to enrollment and various approaches to overcome them. RESULTS: The overall survey response rate was 54% (79/145). Only 29% (23/79) agreed that it is easy to enroll study participants. Regarding patient barriers, 69% (55/79) agreed that HZO patients want to be treated with antiviral medication and 69% (54/78) agreed that HZO patients on antivirals do not want to be randomized. Regarding personal barriers facing investigators, 91% (72/79) agreed that antivirals are effective and 100% that the research questions ZEDS is designed to answer are very important. Fewer than 30% of respondents believed that steps taken to increase enrollment have been very helpful. Over half (54%, 42/78) believed that advertising on social media would be moderately or very effective. CONCLUSIONS: Belief among ZEDS investigators that antivirals are effective, and the preference of patients to be treated with antivirals rather than be randomized in ZEDS, are major barriers to enrollment. New approaches to overcoming barriers are necessary to develop an evidence-based standard of care for treatment of HZO.

Evolution of an Accelerated 3-Year Pathway to the MD Degree: The Experience of New York University Grossman School of Medicine.

The revision of the curriculum at New York University Grossman School of Medicine in 2010, with a reduction of the preclerkship curriculum to 18 months, made it possible to offer an accelerated 3-year pathway in 2013 for students who know their career path. The goals of the program include individualizing education, reducing student debt, and integrating undergraduate and graduate medical education. This accelerated 3-year doctor of medicine (3YMD) pathway is the first program of its kind in the United States to offer conditional acceptance to residency programs in all specialties through the National Resident Matching Program. Since inception of the pathway 6 years ago, 81 students have graduated. Critical components to successfully launch and implement the program are described.Unwavering commitment to the program as a high institutional priority by the dean and vice dean for education facilitated the support required by department chairs and residency program directors and the flexibility needed for success. Alignment between the 3- and 4-year pathways has made it possible to add points of entry into the 3-year pathway during the second and third years and to shift back into the 4-year pathway, as warranted. Modifications to how 3YMD students are mentored included changing the role of the departmental advisor and adding a dedicated 3YMD pathway advisor who serves as an advocate for both the students and the program. Having a relatively large number of 3YMD students has contributed to the success of the program and facilitated acceptance by the residencies.

Current Practice Patterns and Opinions on the Management of Recent-Onset or Chronic Herpes Zoster Ophthalmicus of Zoster Eye Disease Study Investigators.

PURPOSE: To determine practices and opinions among study investigators in the Zoster Eye Disease Study (ZEDS) regarding suppressive valacyclovir treatment for recent-onset and chronic herpes zoster ophthalmicus (HZO). METHODS: An Internet-based survey was distributed to 170 ZEDS study investigators with questions regarding treatment practices for stromal keratitis in HZO and opinions regarding the efficacy of prolonged antiviral prophylaxis. RESULTS: The response rate was 72.4% (123/170). Topical steroids and oral antivirals were used by the majority of respondents for stromal keratitis in both recent-onset (69.1%, 85/123) and chronic HZO (63.4%, 78/123) (P = 0.86). The duration of treatment was similar in both recent-onset and chronic HZO (P = 0.58) with 50.4% (124/246) of ZEDS investigators using prolonged treatment for stromal keratitis due to recent-onset or chronic HZO. The majority of ZEDS respondents believe that oral antivirals are effective during treatment (70.7%, 87/123). CONCLUSIONS: Approximately half of ZEDS investigators treat HZO with prolonged oral antivirals, in addition to topical steroids, and two-thirds believe that it is effective. Completion of ZEDS is feasible and necessary to determine whether or not these practices are effective. Participation in this study is necessary to obtain evidence to support treatment that many ophthalmologists use and believe is effective.

Evaluating Physician Attitudes and Practices Regarding Herpes Zoster Vaccination.

PURPOSE: To investigate the knowledge, attitudes, and practice patterns of primary care physicians regarding administration of the herpes zoster (HZ) vaccine at NYU Langone Health (NYULH). METHODS: A cross-sectional online survey was distributed from January to March 2017 to all physicians in the Division of General Internal Medicine and Clinical Innovation at NYULH across 5 different practice settings. RESULTS: The response rate was 26% (138 of 530). Of the surveyed physicians, 76% (100/132) agreed that the HZ vaccine was an important clinical priority, compared with 93% and 94% for influenza and pneumococcal vaccination, respectively (P < 0.001). Only 35% (47/132) strongly agreed that it was important, compared with 68% (90/132) and 74% (98/132) who strongly agreed that pneumococcal and influenza vaccines, respectively, were important. Respondents estimated that 43% of their immunocompetent patients aged 60 or older received the HZ vaccine, whereas only 11% of patients aged 50 to 59 received the HZ vaccine (P < 0.001). The rate of HZ vaccination was lower in public hospitals (26%) than in the NYULH faculty group practice (46%) (P = 0.007). A greater percent (67% and 72%) of their patients have received influenza and pneumococcal vaccines, respectively (P < 0.001). Almost all doctors (99%, 131/132) consider the Centers for Disease Control and Prevention recommendations important in determining vaccination practices. CONCLUSIONS: HZ vaccination rates remain relatively low compared with rates of influenza and pneumonia vaccination. The recommendation for vaccination against zoster by the Centers for Disease Control and Prevention for individuals aged 50 years and older and stronger recommendations by primary care physicians for administration of zoster vaccines are needed to increase HZ vaccination rates.