Faculty Bibliography

PURPOSE/OBJECTIVE:To report on the presentation, treatment, and visual outcome of stromal keratitis (SK) in the Zoster Eye Disease Study (ZEDS). DESIGN/METHODS:Secondary analysis of SK endpoint of randomized clinical trial. SUBJECTS/METHODS:Herpes Zoster Ophthalmicus (HZO) patients were randomized in a double-masked clinical trial of oral valacyclovir 1g daily or placebo for 1 year. They were followed prospectively every 3 months for 18 months for endpoints of SK, iritis (IR), endothelial keratitis (EK), or dendritiform epithelial keratitis (DEK). METHODS:Presentation of recurrent, new, or worsening SK was evaluated retrospectively by treatment assignment, randomization strata, and use of topical steroids. Investigators had been allowed discretionary treatment of endpoints including open label valacyclovir and topical steroids. Visual outcome and treatment with open label oral valacyclovir and topical steroids were evaluated. MAIN OUTCOME MEASURES/METHODS:Use of open label valacyclovir and topical steroid treatment of recurrent, new, or worsening SK, and visual acuity at 12 months. RESULTS:Recurrent, new, or worsening SK occurred in 105/527(20%) participants. Randomization group was not associated with this complication. Mean best corrected visual acuity at enrollment was logMAR 0.10±0.14 with no difference at 1 year, logMAR 0.13±0.2, and no difference between valacyclovir and placebo groups at enrollment or at 1 year. Among the 105 instances of SK, 79(75%) were recognized at scheduled study visits rather than at episodic visits. In only 11/105(10%) of recurrent, new, or worsening SK, did masked investigators opt to treat with open label oral antiviral. At the time of SK complication, 52/105(50%) were on topical steroid, but 47/52(90%) on topical steroids were using 1x daily or less, 21/47(45%) high potency and 26/47(55%) low potency (p=0.47). Of 48/105(47%) on no topical steroids at recurrent, new, or worsening SK, 18/48(38%) had discontinued steroids in the prior 3 months. 38/48(75%) on no topical steroids at complication SK were subsequently treated with high potency steroids 2x daily or more. Of 26/52(50%) on low potency steroids at complication SK, 23/26(88%) were treated with increase in frequency only. CONCLUSIONS:Individuals with ocular complications of HZO who develop SK generally maintain very good vision without use of oral antiviral therapy when monitored closely and SK is recognized and treated. Low potency topical steroids should be considered for treatment and ongoing suppression of SK in HZO.

OBJECTIVE:Poor sleep and obstructive sleep apnea (OSA) are prevalent among transportation workers. METHODS:45 transportation workers from worksites in the Northeast US completed surveys assessing 1) sleepiness, 2) OSA, and 3) OSA stage of change, then participated in focus groups or interviews. RESULTS:Participants were 93.2% male, 90.1% white non-Hispanic. 77.8% scored high risk for OSA, while 11.1% of those at risk reported an OSA diagnosis. Only 31.4% of high risk participants reported having contemplated OSA evaluation or treatment. Qualitative themes pertained to difficulty unwinding, uncertain work hours, fears about and barriers to OSA treatment, and misinformation about OSA. CONCLUSIONS:Results reveal a high prevalence of OSA risk and a low rate of diagnosis and OSA readiness to change. We identify themes for future interventions to improve awareness about OSA among transportation workers.

Osteoarthritis, especially knee osteoarthritis, is a leading cause of disability and reduced quality of life. The etiology of pain in osteoarthritis is multifactorial, and one promising potential treatment approach involves targeting chemokine systems. The present study was a phase 2, multisite, multiperiod randomized crossover trial of CNTX-6970, a small molecule and selective oral cytokine chemokine receptor type 2 (CCR2) and CCR5 antagonist, in patients with painful knee osteoarthritis (OA). It represents the first trial performed within the National Institutes of Health's Early Phase Pain Investigation Clinical Network. The primary objectives were to evaluate the safety and efficacy of CNTX-6970, relative to placebo, for the treatment of moderate to severe pain related to knee OA. A total of 55 participants were randomized in this multiperiod crossover trial. Linear mixed effects models revealed no significant pain-related benefits of active medication; indeed, trial participants reported slightly higher knee pain intensity when taking the novel chemokine antagonist CNTX-6970 than when taking placebo. In addition, biomarker analysis revealed notably higher level of serum monocyte chemoattractant protein 1 levels when patients were on CNTX-6970 compared to placebo. Overall, although CNTX-6970 was safe and relatively well-tolerated, pharmacologic blockade of specific chemokine receptors with this compound was not effective in reducing moderate-to-severe knee osteoarthritis pain.

BACKGROUND:Nonadherence to antihypertensive medications is common. Mobile health (mHealth)-based behavioral economic interventions may improve adherence, but remain largely untested, especially in vulnerable populations. OBJECTIVE:The study sought to test whether an mHealth incentive lottery would lower systolic blood pressure (SBP) and improve adherence. METHODS:BETTER-BP (Behavioral Economics Trial To Enhance Regulation of Blood Pressure) was a randomized trial conducted in 3 safety-net clinics in New York City. Eligible participants were adults with hypertension prescribed at least 1 antihypertensive medication, with SBP >140 mm Hg, and poor self-reported adherence. In the intervention arm, an incentive lottery was administered via SMS messaging. All participants received passive adherence monitoring. The intervention lasted 6 months, with continued monitoring until 12 months. The primary clinical endpoint was change in SBP at 6 months. The primary process endpoint was adequate antihypertensive medication adherence (≥80% days adherent) from baseline to 6 months. RESULTS:Four-hundred participants (265 intervention:135 control) were enrolled with median age 57 years, 60.5% women, 61.5% Hispanic, and 20.3% non-Hispanic Black. Over 70% had Medicaid or no insurance. At 6 months, intervention arm participants were twice as likely to achieve adequate adherence (71% vs 34%; adjusted risk ratio: 2.04; 95% CI: 1.58-2.63), but there was no significant change in mean SBP (-6.7 mm Hg intervention vs -5.8 mm Hg control; P = 0.62). From 6 to 12 months, adherence was similar (31% intervention vs 26% control; adjusted risk ratio: 1.17; 95% CI: 0.83-1.65). CONCLUSIONS:In a diverse safety-net population, the BETTER-BP intervention doubled the rate of adequate antihypertensive medication adherence but did not reduce SBP at 6 months.

Longitudinal trajectories of Long COVID remain ill-defined, yet are critically needed to advance clinical trials, patient care, and public health initiatives for millions of individuals with this condition. Long COVID trajectories were determined prospectively among 3,659 participants (69% female; 99.6% Omicron era) in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Adult Cohort. Finite mixture modeling was used to identify distinct longitudinal profiles based on a Long COVID research index measured 3 to 15 months after infection. Eight longitudinal profiles were identified. Overall, 195 (5%) had persistently high Long COVID symptom burden, 443 (12%) had non-resolving, intermittently high symptom burden, and 526 (14%) did not meet criteria for Long COVID at 3 months but had increasing symptoms by 15 months, suggestive of distinct pathophysiologic features. At 3 months, 377 (10%) met the research index threshold for Long COVID. Of these, 175 (46%) had persistent Long COVID, 132 (35%) had moderate symptoms, and 70 (19%) appeared to recover. Identification of these Long COVID symptom trajectories is critically important for targeting enrollment for future studies of pathophysiologic mechanisms, preventive strategies, clinical trials and treatments.