Faculty Bibliography

INTRODUCTION/UNASSIGNED:Excessive dialytic potassium (K) and acid removal are risk factors for arrhythmias; however, treatment-to-treatment dialysate modification is rarely performed. We conducted a multicenter, pilot randomized study to test the safety, feasibility, and efficacy of 4 point-of-care (POC) chemistry-guided protocols to adjust dialysate K and bicarbonate (HCO3) in outpatient hemodialysis (HD) clinics. METHODS/UNASSIGNED:Participants received implantable cardiac loop monitors and crossed over to four 4-week periods with adjustment of dialysate K or HCO3 at each treatment according to pre-HD POC values: (i) K-removal minimization, (ii) K-removal maximization, (iii) Acidosis avoidance, and (iv) Alkalosis avoidance. The primary end point was percentage of treatments adhering to the intervention algorithm. Secondary endpoints included pre-HD K and HCO variability, adverse events, and rates of clinically significant arrhythmias (CSAs). RESULTS/UNASSIGNED:Nineteen subjects were enrolled in the study. HD staff completed POC testing and correctly adjusted the dialysate in 604 of 708 (85%) of available HD treatments. There was 1 K ≤3, 29 HCO3 <20 and 2 HCO3 >32 mEq/l and no serious adverse events related to study interventions. Although there were no significant differences between POC results and conventional laboratory measures drawn concurrently, intertreatment K and HCO3 variability was high. There were 45 CSA events; most were transient atrial fibrillation (AF), with numerically fewer events during the alkalosis avoidance period (8) and K-removal maximization period (3) compared to other intervention periods (17). There were no significant differences in CSA duration among interventions. CONCLUSION/UNASSIGNED:Algorithm-guided K/HCO3 adjustment based on POC testing is feasible. The variability of intertreatment K and HCO3 suggests that a POC-laboratory-guided algorithm could markedly alter dialysate-serum chemistry gradients. Definitive end point-powered trials should be considered.

OBJECTIVE:Children with high-frequency severe-to-profound hearing loss and low-frequency residual hearing who do not derive significant benefit from hearing aids are now being considered for cochlear implantation. Previous research shows that hearing preservation is possible and may be desirable for the use of electroacoustic stimulation (EAS) in adults, but this topic remains underexplored in children. The goal of this study was to explore factors relating to hearing preservation, acceptance, and benefits of EAS for children. STUDY DESIGN:Retrospective review. SETTING:Tertiary academic medical center. PATIENTS:Forty children (48 ears) with preoperative low-frequency pure-tone averages of 75 dB HL or less at 250 and 500 Hz (n = 48). INTERVENTION:All patients underwent cochlear implantation with a standard-length electrode. MAIN OUTCOME MEASURE:Low-frequency audiometric thresholds, speech perception, and EAS usage were measured at initial stimulation, and 3 and 12 months postoperatively. Outcomes were compared between children with and without hearing preservation, and between EAS users and nonusers. RESULTS:Hearing was preserved at similar rates as adults but worse for children with an enlarged vestibular aqueduct. Fewer than half of children who qualified to use EAS chose to do so, citing a variety of audiologic and nonaudiologic reasons. No differences were detected in speech perception scores across the groups for words, sentences, or sentences in noise tests. CONCLUSIONS:Neither hearing preservation nor EAS use resulted in superior speech perception in children with preoperative residual hearing; rather, all children performed well after implantation.

Covariate balance is crucial in obtaining unbiased estimates of treatment effects in observational studies. Methods that target covariate balance have been successfully proposed and largely applied to estimate treatment effects on continuous outcomes. However, in many medical and epidemiological applications, the interest lies in estimating treatment effects on time-to-event outcomes. With this type of data, one of the most common estimands of interest is the marginal hazard ratio of the Cox proportional hazards model. In this article, we start by presenting robust orthogonality weights, a set of weights obtained by solving a quadratic constrained optimization problem that maximizes precision while constraining covariate balance defined as the correlation between confounders and treatment. By doing so, robust orthogonality weights optimally deal with both binary and continuous treatments. We then evaluate the performance of the proposed weights in estimating marginal hazard ratios of binary and continuous treatments with time-to-event outcomes in a simulation study. We finally apply robust orthogonality weights in the evaluation of the effect of hormone therapy on time to coronary heart disease and on the effect of red meat consumption on time to colon cancer among 24,069 postmenopausal women enrolled in the Women's Health Initiative observational study.

Objectives: The prevalence and incidence of SARS-CoV-2, the virus which causes COVID-19, at any given time remains controversial, and is an essential piece in understanding the dynamics of the epidemic. Cross-sectional studies and single time point testing approaches continue to struggle with appropriate adjustment methods for the high false positive rates in low prevalence settings or high false negative rates in high prevalence settings, and post-hoc adjustment at the group level does not fully address this issue for incidence even at the population level. Methods: In this study, we use seroprevalence as an illustrative example of the benefits of using a case definition using a combined parallel and serial testing framework to confirm antibody-positive status. In a simulation study, we show that our proposed approach reduces bias and improves positive and negative predictive value across the range of prevalence compared with cross-sectional testing even with gold standard tests and post-hoc adjustment. Using data from the North Carolina COVID-19 Community Research Partnership, we applied the proposed case definition to the estimation of SARS-CoV-2 seroprevalence and incidence early in the pandemic. Results: The proposed approach is not always feasible given the cost and time required to administer repeated tests; however, it reduces bias in both low and high prevalence settings and addresses misclassification at the individual level. This approach can be applied to almost all testing contexts and platforms. Conclusions: This systematic approach offers better estimation of both prevalence and incidence, which is important to improve understanding and facilitate controlling the pandemic.

Well-regulated clinical trials have shown FDA-approved COVID-19 vaccines to be immunogenic and highly efficacious. We evaluated seroconversion rates in adults reporting ≥ 1 dose of an mRNA COVID-19 vaccine in a cohort study of nearly 8000 adults residing in North Carolina to validate immunogenicity using a novel approach: at-home, participant administered point-of-care testing. Overall, 91.4% had documented seroconversion within 75 days of first vaccination (median: 31 days). Participants who were older and male participants were less likely to seroconvert (adults aged 41-65: adjusted hazard ratio [aHR] 0.69 [95% confidence interval (CI): 0.64, 0.73], adults aged 66-95: aHR 0.55 [95% CI: 0.50, 0.60], compared to those 18-40; males: aHR 0.92 [95% CI: 0.87, 0.98], compared to females). Participants with evidence of prior infection were more likely to seroconvert than those without (aHR 1.50 [95% CI: 1.19, 1.88]) and those receiving BNT162b2 were less likely to seroconvert compared to those receiving mRNA-1273 (aHR 0.84 [95% CI: 0.79, 0.90]). Reporting at least one new symptom after first vaccination did not affect time to seroconversion, but participants reporting at least one new symptom after second vaccination were more likely to seroconvert (aHR 1.11 [95% CI: 1.05, 1.17]). This data demonstrates the high community-level immunogenicity of COVID-19 vaccines, albeit with notable differences in older adults, and feasibility of using at-home, participant administered point-of-care testing for community cohort monitoring. Trial registration: ClinicalTrials.gov NCT04342884.

OBJECTIVE:To review the current literature regarding cochlear implantation in patients with retrocochlear pathologies and extract speech perception scores between 6 months and 1 year after surgery. DATABASES REVIEWED/UNASSIGNED:PubMed/MEDLINE, Embase and Cochrane CENTRAL via Ovid, CINAHL Complete via Ebsco, and Web of Science. METHODS:The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search strategies included keywords and subject headings to maximize retrieval and reflect cochlear implants and retrocochlear pathologies. Patients with previously resected vestibular schwannoma (VS) were excluded. RESULTS:There were 2,524 abstracts screened against inclusion criteria, and 53 studies were included, with individual data available for 171 adult patients. Pathologies included were either observed or irradiated VS (previously operated tumors were excluded) (n = 99, 57.9%), superficial siderosis (n = 39, 22.8%), neurosarcoidosis (n = 11, 6.4%), and previous central nervous system or skull base radiation (n = 22, 12.9%). Mean (standard deviation) postoperative consonant-nucleus-consonant (CNC) word scores were 45.4% (24.2) for observed VS, 44.4% (20.8) for irradiated VS, 43.6% (21.0) for superficial siderosis, 89.5% (3.0) for neurosarcoidosis, and 30.0% (30.2) in patients with previous central nervous system or skull base irradiation. Irradiated compared with observed VS had similar postoperative CNC word scores (effect size, 0.06; p = 0.71). Age, sex, maximal tumor dimension, and neurofibromatosis type 2 status did not significantly impact cochlear implant performance in patients with VS. Eighty-two percent of patients with reported device usage were daily users, and overall, 82% of cases benefitted from cochlear implantation. CONCLUSION/CONCLUSIONS:Cochlear implantation in patients with concomitant retrocochlear pathology generally results in improved speech discrimination scores sustained over time.

BACKGROUND:Delayed-onset of headache seems a specific feature of cerebrovascular events after COVID-19 vaccines. METHODS:All consecutive events reported to the United States Vaccine Adverse Reporting System following COVID-19 vaccines (1 January to 24 June 2021), were assessed. The timing of headache onset post-vaccination in subjects with and without concomitant cerebrovascular events, including cerebral venous thrombosis, ischemic stroke, and intracranial haemorrhage was analysed. The diagnostic accuracy in predicting concurrent cerebrovascular events of the guideline- proposed threshold of three-days from vaccination to headache onset was evaluated. RESULTS:There were 314,610 events following 306,907,697 COVID-19 vaccine doses, including 41,700 headaches, and 178/41,700 (0.4%) cerebrovascular events. The median time between the vaccination and the headache onset was shorter in isolated headache (1 day vs. 4 (in cerebral venous thrombosis), 3 (in ischemic stroke), or 10 (in intracranial hemorrhage) days, all P < 0.001). Delayed onset of headache had an area under the curve of 0.83 (95% CI: 0.75-0.97) for cerebral venous thrombosis, 0.70 (95% CI: 0.63-76) for ischemic stroke and 0.76 (95% CI: 0.67-84) for intracranial hemorrhage, and >99% negative predictive value. CONCLUSION/CONCLUSIONS:Headache following COVID-19 vaccination occurs within 1 day and is rarely associated with cerebrovascular events. Delayed onset of headache 3 days post-vaccination was an accurate diagnostic biomarker for the occurrence of a concomitant cerebrovascular events.

OBJECTIVE:To identify the rates of neurological events following administration of mRNA (Pfizer, Moderna) or adenovirus vector (Janssen) vaccines in the U.S.. METHODS:We utilized publicly available data from the U.S. Vaccine Adverse Event Reporting System (VAERS) collected between January 1, 2021-June 14, 2021. All free text symptoms that were reported within 42 days of vaccine administration were manually reviewed and grouped into 36 individual neurological diagnostic categories. Post-vaccination neurological event rates were compared between vaccine types and to age-matched baseline incidence rates in the U.S. and rates of neurological events following COVID. RESULTS:Of 306,907,697 COVID vaccine doses administered during the study timeframe, 314,610 (0.1%) people reported any adverse event and 105,214 (0.03%) reported neurological adverse events in a median of 1 day (IQR0-3) from inoculation. Guillain-Barre Syndrome (GBS), and cerebral venous thrombosis (CVT) occurred in fewer than 1 per 1,000,000 doses. Significantly more neurological adverse events were reported following Janssen (Ad26.COV2.S) vaccination compared to either Pfizer-BioNtech (BNT162b2) or Moderna (mRNA-1273; 0.15% versus 0.03% versus 0.03% of doses, respectively,P<0.0001). The observed-to-expected ratios for GBS, CVT and seizure following Janssen vaccination were ≥1.5-fold higher than background rates. However, the rate of neurological events after acute SARS-CoV-2 infection was up to 617-fold higher than after COVID vaccination. INTERPRETATION/CONCLUSIONS:Reports of serious neurological events following COVID vaccination are rare. GBS, CVT and seizure may occur at higher than background rates following Janssen vaccination. Despite this, rates of neurological complications following acute SARS-CoV-2 infection are up to 617-fold higher than after COVID vaccination. This article is protected by copyright. All rights reserved.

The double burden of HIV/AIDS and tuberculosis (TB), coupled with endemic and problematic food insecurity in Africa, can interact to negatively impact health outcomes, creating a syndemic. For people living with HIV/AIDS (PWH), food insecurity is a significant risk factor for acquiring TB due to the strong nutritional influences and co-occurring contextual barriers. We aim to synthesize evidence on the syndemic relationship between HIV/AIDS and TB co-infection and food insecurity in Africa. We conducted a scoping review of studies in Africa that included co-infected adults and children, with evidence of food insecurity, characterized by insufficient to lack of access to macronutrients. We sourced information from major public health databases. Qualitative, narrative analysis was used to synthesize the data. Of 1072 articles screened, 18 articles discussed the syndemic effect of HIV/AIDS and TB co-infection and food insecurity. Reporting of food insecurity was inconsistent, however, five studies estimated it using a validated scale. Food insecure co-infected adults had an average BMI of 16.5-18.5 kg/m². Negative outcomes include death (n = 6 studies), depression (n = 1 study), treatment non-adherence, weight loss, wasting, opportunistic infections, TB-related lung diseases, lethargy. Food insecurity was a precursor to co-infection, especially with the onset/increased incidence of TB in PWH. Economic, social, and facility-level factors influenced the negative impact of food insecurity on the health of co-infected individuals. Nutritional support, economic relief, and psychosocial support minimized the harmful effects of food insecurity in HIV-TB populations. Interventions that tackle one or more components of a syndemic interaction can have beneficial effects on health outcomes and experiences of PWH with TB in Africa.