Faculty Bibliography

IMPORTANCE/UNASSIGNED:Evidence regarding suppressive valacyclovir treatment on postherpetic neuralgia is necessary to guide care. OBJECTIVE/UNASSIGNED:To test the hypothesis that suppressive treatment with 1000 mg/d of oral valacyclovir for 12 months reduces the prevalence, severity, and duration of postherpetic neuralgia compared with placebo at 12 and 18 months in participants with herpes zoster ophthalmicus (HZO). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Multicenter, placebo-controlled randomized clinical trial including 527 immunocompetent, nonpregnant adults with history of HZO rash, documented keratitis, or iritis within 1 year and an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater. The study was conducted at 95 participating sites (in Canada, New Zealand, and the US) from November 2017 to June 2024 and participant visits occurred every 3 months. INTERVENTION/UNASSIGNED:Treatment with 1000 mg/d of valacyclovir or placebo for 12 months. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Prevalence of postherpetic neuralgia, severity as determined by pain score (a score of ≥3 on a scale of 1-10), pain duration (≥3 months after HZO onset), and total daily dose of pain medication. RESULTS/UNASSIGNED:Of the 527 participants (490 completed 12 months of treatment and 460 completed 18 months), 73 (14%) had postherpetic neuralgia and were analyzed by age at HZO onset (<60 years or ≥60 years) and disease duration (recent [<6 months] or chronic [≥6 months]). Of the 73 participants with postherpetic neuralgia (34 in the valacyclovir group and 39 in the placebo group), the mean age was 62.4 years (SD, 13.6 years), 59% were female, 5% were Black or African American, and 10% were Hispanic. The prevalence of postherpetic neuralgia at 12 months was not reduced by valacyclovir (12/32 [38%]) compared with placebo (14/35 [40%]) (between-group difference, 2.5% [95% CI, -20.8% to 25.8%]; P>.99). The participants who were younger than 60 years at HZO onset and had a chronic disease duration had lower pain scores in the valacyclovir group (mean score, 0.3 [SD, 0.9]) vs the placebo group (mean score, 0.8 [SD, 1.9]) at 12 months (P = .045) and at 18 months (mean score, 0.2 [SD, 0.9] vs 1.0 [SD, 2.3], respectively; P = .02). There was a decrease in pain duration in the valacyclovir group at 18 months (mean, 13.6 [SD, 11.4] months) vs the placebo group (mean, 18.7 [SD, 29.5] months) (linear mixed-effects model between-group difference, -3.39 months [95% CI, -6.73 to -0.04 months]; P = .046). The total daily dose of neuropathic pain medication was lower in the valacyclovir group (mean, 271.4 [SD, 593.8] mg/d) vs the placebo group (mean, 363.4 [SD, 592.2] mg/d) at 12 months (linear mixed-effects model P = .006) and at 18 months (mean, 209.0 [SD, 412.8] mg/d vs 286.2 [SD, 577.9] mg/d, respectively; linear mixed-effects model P = .01). CONCLUSIONS AND RELEVANCE/UNASSIGNED:One year of suppressive treatment with valacyclovir was associated with a lower dosage of neuropathic pain medication. Participants in the valacyclovir group, who were younger at HZO onset and had a chronic disease duration, had lower pain scores. These secondary outcomes support consideration of 1 year of suppressive treatment with valacyclovir to reduce dosage of pain medications and pain due to HZO. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03134196.

IMPORTANCE/UNASSIGNED:High-quality evidence regarding suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) is necessary to guide care. OBJECTIVE/UNASSIGNED:To determine whether suppressive valacyclovir compared with placebo delays the occurrence of new or worsening stromal keratitis (SK), endothelial keratitis (EK), iritis, or dendriform epithelial keratitis (DEK) during 12 months of treatment and if treatment benefit persisted at 18 months (secondary end point). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Zoster Eye Disease Study (ZEDS) was a randomized clinical trial conducted in 95 sites from November 2017 to June 2024. Immunocompetent, nonpregnant adults with a history of an HZO rash, documented active keratitis or iritis within 1 year, and an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater were eligible. After determined to be eligible, participants were randomized in 4 strata: age at onset (<60 years vs ≥60 years) and disease duration (<6 months vs ≥6 months). INTERVENTIONS/UNASSIGNED:A total of 12 months of double-masked daily valacyclovir, 1000 mg, or placebo. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was time to first occurrence within 12 months of new or worsening SK, EK, iritis, or DEK. RESULTS/UNASSIGNED:A total of 527 participants (median [IQR] age, 60 [50-68] years; 266 female [50.5%]; 266 in the valacyclovir group; 261 in the placebo group) were randomized in 4 strata; 481 completed 12 months, and 460 completed 18 months. Data were analyzed by intention to treat. At 12 months, primary end points occurred in 86 participants (33%) assigned to placebo and 74 (28%) assigned to valacyclovir, and at 18 months in 104 participants (40%) assigned to placebo and 86 (32%) assigned to valacyclovir. The hazard ratio (HR) of the primary end point at 12 months was 0.77 for participants taking valacyclovir vs placebo (HR, 0.77; adjusted 95% CI, 0.56-1.05; P = .09) and 0.73 at the secondary end point at 18 months (HR, 0.73; adjusted 95% CI, 0.55-0.97; P = .03). There was a reduction of multiple other secondary end points at 12 months (HR, 0.70; 95% CI, 0.52-0.95; P = .02) and 18 months (HR, 0.72; 95% CI, 0.55-0.95; P = .02). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Although the primary outcome did not show a benefit of suppressive valacyclovir treatment, secondary study outcomes showed treatment superiority at the 18-month end point and reduced number of multiple episodes of keratitis or iritis at both 12 and 18 months. These results support consideration of 1 year of suppressive valacyclovir treatment for HZO. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03134196.

Acne is a common skin condition, but little data exist on the comparative efficacy of topical acne therapies. We conducted a systematic review and network meta-analysis to evaluate the efficacy of topical therapies for mild-to-moderate acne. Searches in PubMed/MEDLINE, Cochrane CENTRAL via Ovid, Embase via Ovid and Web of Science were conducted on 29 November 2021. Randomized controlled trials examining ≥12 weeks of topical treatments for acne vulgaris in subjects aged 12 and older were included. Main outcomes were absolute or percent change in acne lesion count and treatment success on the Investigator's Global Assessment scale. Thirty-five randomized clinical trials with 33,472 participants comparing nine different topical agents were included. Adapalene-benzoyl peroxide (BPO), clindamycin-BPO and clindamycin-tretinoin demonstrated the greatest reduction in non-inflammatory (ratio of means [RoM] 1.76; 95% CI [1.46; 2.12], RoM 1.70; 95% CI [1.44; 2.02] and RoM 1.87; 95% CI [1.53; 2.30], respectively), inflammatory (RoM 1.56; 95% CI [1.44; 1.70], RoM 1.49; 95% CI [1.39; 1.60] and RoM 1.48; 95% CI [1.36; 1.61], respectively) and total lesion count (ROM 1.67; 95% CI [1.47; 1.90], RoM 1.59; 95% CI [1.42; 1.79] and RoM 1.64; 95% CI [1.42; 1.89], respectively) compared to placebo. All single agents outperformed placebo except tazarotene, which did not significantly outperform placebo for inflammatory and non-inflammatory lesion count reduction. Most combination agents significantly outperformed their individual components in lesion count reduction and global assessment scores, except for clindamycin-tretinoin and clindamycin-BPO, which did not significantly outperform tretinoin (RoM 1.13; 95% CI [0.94; 1.36]) and BPO (RoM = 1.15, 95% CI [0.98; 1.36]), respectively, for non-inflammatory lesion reduction. There was no significant difference amongst most single agents when evaluating lesion count reduction. Combination agents are generally most effective for mild-to-moderate acne; however for non-inflammatory acne, the addition of clindamycin in topical regimens is unnecessary and should be avoided.

BACKGROUND:Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores. METHODS:BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase. RESULTS:Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20 mg of ropivacaine plus 4 mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection). CONCLUSIONS:The trial has a primary efficacy end point (oral morphine equivalent/day use within 24 h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48 h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.

IMPORTANCE/UNASSIGNED:Among older adults with ischemic heart disease, participation in traditional ambulatory cardiac rehabilitation (CR) remains low. While mobile health CR (mHealth-CR) provides a novel opportunity to deliver care, age-specific impairments to technology use may limit uptake, and efficacy data are currently lacking. OBJECTIVE/UNASSIGNED:To test whether mHealth-CR improves functional capacity in older adults. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The RESILIENT phase 2, multicenter, randomized clinical trial recruited patients aged 65 years or older with ischemic heart disease (defined as a hospital visit for myocardial infarction or coronary revascularization) from 5 academic hospitals in New York, Connecticut, and Massachusetts between January 9, 2020, and April 22, 2024. INTERVENTION/UNASSIGNED:Participants were randomized 3:1 to mHealth-CR or usual care. mHealth-CR consisted of commercially available software delivered on a tablet computer, coupled with remote monitoring and weekly exercise therapist telephone calls, delivered over a 3-month duration. As RESILIENT was a trial conducted in a routine care setting to inform decision-making, participants in both arms were also allowed to receive traditional CR at their cardiologist's discretion. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was change from baseline to 3 months in functional capacity, measured by 6-minute walk distance (6MWD). Secondary outcomes were health status (12-Item Short Form Health Survey [SF-12]), residual angina, and impairment in activities of daily living. RESULTS/UNASSIGNED:A total of 400 participants (median age, 71.0 years [range, 65.0-91.0 years]; 291 [72.8%] male) were randomized to mHealth-CR (n = 298) or usual care (n = 102) and included in the intention-to-treat analysis. Of those, 356 participants (89.0%) returned in person for 6MWD assessment at 3 months. For the primary outcome, there was no adjusted difference in 6MWD between participants receiving mHealth-CR vs usual care (15.6 m; 95% CI, -0.3 to 31.5 m; P = .06). Among subgroups, there was an improvement in 6MWD among women (36.6 m; 95% CI, 8.7-64.4 m). There were no differences in any secondary outcomes between groups (eg, adjusted difference in SF-12 physical component scores at 3 months: -1.9 points; 95% CI, -3.9 to 0.2 points). Based on inverse propensity score weighting, there was no effect of mHealth-CR on 6MWD among those who did not attend traditional CR (25.7 m; 95% CI, -8.7 to 60.2 m). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial of mHealth-CR vs usual care, mHealth-CR did not significantly increase 6MWD or result in improvements in secondary outcomes. The findings suggest the older adult population may require more age-tailored mHealth strategies to effectively improve outcomes. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03978130.

BACKGROUND:In cohort studies with time-to-event outcomes, covariates of interest often have values that change over time. The classical Cox regression model can handle time-dependent covariates but assumes linear effects on the log hazard function, which can be limiting in practice. Furthermore, when multiple correlated covariates are studied, it is of great interest to model their joint effects by allowing a flexible functional form and to delineate their relative contributions to survival risk. METHODS:Motivated by the World Trade Center (WTC)-exposed Fire Department of New York cohort study, we proposed a partial-linear single-index Cox (PLSI-Cox) model to investigate the effects of repeatedly measured metabolic syndrome indicators on the risk of developing WTC lung injury associated with particulate matter exposure. The PLSI-Cox model reduces the dimensionality of covariates while providing interpretable estimates of their effects. The model's flexible link function accommodates nonlinear effects on the log hazard function. We developed an iterative estimation algorithm using spline techniques to model the nonparametric single-index component for potential nonlinear effects, followed by maximum partial likelihood estimation of the parameters. RESULTS:Extensive simulations showed that the proposed PLSI-Cox model outperformed the classical time-dependent Cox regression model when the true relationship was nonlinear. When the relationship was linear, both the PLSI-Cox model and classical time-dependent Cox regression model performed similarly. In the data application, we found a possible nonlinear joint effect of metabolic syndrome indicators on survival risk. Among the different indicators, BMI had the largest positive effect on the risk of developing lung injury, followed by triglycerides. CONCLUSION/CONCLUSIONS:The PLSI-Cox models allow for the evaluation of nonlinear effects of covariates and offer insights into their relative importance and direction. These methods provide a powerful set of tools for analyzing data with multiple time-dependent covariates and survival outcomes, potentially offering valuable insights for both current and future studies.

BACKGROUND:The optimal management of patients with intermediate-risk pulmonary embolism (PE), who have right heart dysfunction (determined by a combination of imaging and cardiac biomarkers) but a normal blood pressure, is uncertain. These patients suffer from reduced functional capacity and a lower quality of life over the long-term, despite use of anticoagulant therapy. Catheter-directed therapy (CDT) is a promising treatment for acute PE that rapidly removes thrombus and potentially improves cardiac dysfunction. However, CDT has risk and is costly, and it is not known whether it improves long-term cardiorespiratory fitness and/or quality of life compared with anticoagulation alone. METHODS:) with cardiopulmonary exercise testing at 3 months and reduce New York Heart Association (NYHA) Class at 12 months compared with No-CDT. These 2 primary efficacy outcomes will be analyzed sequentially using a "gatekeeping" procedure; for NYHA class to be compared, peak oxygen consumption must first be shown to be significantly increased by CDT. Safety and cost-effectiveness will also be assessed. CONCLUSION/CONCLUSIONS:When completed, PE-TRACT will provide important evidence regarding the benefits and risks of CDT to treat intermediate-risk PE compared with anticoagulation alone. TRIAL REGISTRATION/BACKGROUND:clinicaltrials.gov: NCT05591118.

PURPOSE/OBJECTIVE: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/METHODS:The study was set at 95 participating clinical centers in 33 states, Canada, and New Zealand. STUDY POPULATION/METHODS: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/METHODS: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/BACKGROUND:ClinicalTrials.gov Identifier: NCT03134196.

BACKGROUND:Asian Americans have the lowest colorectal cancer screening uptake of any racial and ethnic group in the United States. Asian Indians are among the most under-screened Asian American subgroups, but there is limited data for this population. We sought to characterize predictors of colonoscopy use among Asian Indians in New York City. METHODS:Using 2003 to 2016 data from the New York City Community Health Survey, we identified all Asian Indian participants aged 50 years or older. We examined the association between sociodemographic and medical factors and up-to-date colonoscopy use (defined as colonoscopy within the last 10 y) using logistic regression over 4 time periods: 2003 to 2008, 2009 to 2012, 2013 to 2014, 2015 to 2016. RESULTS:On multivariable analysis, language, age, income, recent exercise, body mass index, and influenza vaccination were associated with colonoscopy uptake in 1 time period. Compared with participants who preferred English, those who preferred an Indian language were less likely to have been up-to-date in 2013 to 2014 (odds ratio 0.12, 95% CI 0.02-0.66). Individuals older than 65 years were more likely than those aged 50 to 64 years to have received a colonoscopy in 2009 to 2012 (odds ratio 3.91, 95% CI 1.49-10.24), although the risk estimates were also consistently positive in the other 3 time periods. CONCLUSIONS:Among Asian Indians living in New York City, several demographic, socioeconomic, and health-related characteristics predict colonoscopy use. These findings highlight the importance of examining determinants of colonoscopy uptake in this understudied population to inform future public health interventions.