Faculty Bibliography

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.

Age is an important patient characteristic that has been correlated with specific outcomes after lumbar spine surgery. We performed a retrospective cohort study to model the effect of age on discharge destination and complications after a 1-level or multi-level lumbar spine fusion surgery. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients who underwent lumbar spinal fusion surgery from 2013 through 2017. Perioperative outcomes were compared across ages 18 to 90 using multivariable nonlinear logistic regressioncontrolling for preoperative characteristics. A total of 61,315 patients were analyzed, with patients over 70 having a higher risk of being discharged to an inpatient rehabilitation center and receiving an intraoperative or postoperative blood transfusion. However, the rates of the other complications and outcomes analyzed in this study were not significantly different as patients age. In conclusion, advanced-age affects the discharge destination after a one- or multi-level fusion and intraoperative/postoperative blood transfusion after a one-level fusion. However, age alone does not significantly affect the risk of the other complications and outcomes assessed in this study. This study will help guide preoperative discussion with advanced-aged patients who are considering a 1-level or multi-level lumbar spine fusion surgery.

OBJECTIVE:Spine surgery is especially susceptible to malpractice claims. Critics of the US medical liability system argue that it drives up costs, whereas proponents argue it deters negligence. Here, the authors study the relationship between malpractice claim density and outcomes. METHODS:The following methods were used: 1) the National Practitioner Data Bank was used to determine the number of malpractice claims per 100 physicians, by state, between 2005 and 2010; 2) the Nationwide Inpatient Sample was queried for spinal fusion patients; and 3) the Area Resource File was queried to determine the density of physicians, by state. States were categorized into 4 quartiles regarding the frequency of malpractice claims per 100 physicians. To evaluate the association between malpractice claims and death, discharge disposition, length of stay (LOS), and total costs, an inverse-probability-weighted regression-adjustment estimator was used. The authors controlled for patient and hospital characteristics. Covariates were used to train machine learning models to predict death, discharge disposition not to home, LOS, and total costs. RESULTS:Overall, 549,775 discharges following spinal fusions were identified, with 495,640 yielding state-level information about medical malpractice claim frequency per 100 physicians. Of these, 124,425 (25.1%), 132,613 (26.8%), 130,929 (26.4%), and 107,673 (21.7%) were from the lowest, second-lowest, second-highest, and highest quartile states, respectively, for malpractice claims per 100 physicians. Compared to the states with the fewest claims (lowest quartile), surgeries in states with the most claims (highest quartile) showed a statistically significantly higher odds of a nonhome discharge (OR 1.169, 95% CI 1.139-1.200), longer LOS (mean difference 0.304, 95% CI 0.256-0.352), and higher total charges (mean difference [log scale] 0.288, 95% CI 0.281-0.295) with no significant associations for mortality. For the machine learning models-which included medical malpractice claim density as a covariate-the areas under the curve for death and discharge disposition were 0.94 and 0.87, and the R2 values for LOS and total charge were 0.55 and 0.60, respectively. CONCLUSIONS:Spinal fusion procedures from states with a higher frequency of malpractice claims were associated with an increased odds of nonhome discharge, longer LOS, and higher total charges. This suggests that medicolegal climate may potentially alter practice patterns for a given spine surgeon and may have important implications for medical liability reform. Machine learning models that included medical malpractice claim density as a feature were satisfactory in prediction and may be helpful for patients, surgeons, hospitals, and payers.

BACKGROUND:People who inject drugs (PWID) frequently engage in injection risk behaviours exposing them to blood-borne infections. Understanding the underlying causes that drive various types and levels of risk behaviours is important to better target preventive interventions. METHODS:A total of 2150 PWID in Swedish remand prisons were interviewed between 2002 and 2012. Questions on socio-demographic and drug-related variables were asked in relation to the following outcomes: Having shared injection drug solution and having lent out or having received already used drug injection equipment within a 12 month recall period. RESULTS:Women shared solutions more than men (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.03; 2.21). Those who had begun to inject drugs before age 17 had a higher risk (OR 1.43, 95% CI 0.99; 2.08) of having received used equipment compared to 17-19 year olds. Amphetamine-injectors shared solutions more than those injecting heroin (OR 2.43, 95% CI 1.64; 3.62). A housing contract lowered the risk of unsafe injection by 37-59% compared to being homeless. CONCLUSIONS:Women, early drug debut, amphetamine users and homeless people had a significantly higher level of injection risk behaviour and need special attention and tailored prevention to successfully combat hepatitis C and HIV transmission among PWID. TRIAL REGISTRATION:ClinicalTrials.gov Identifier, NCT02234167.

BACKGROUND:Switch from first line antiretroviral therapy (ART) to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART. MATERIAL AND METHODS/METHODS:Data from 869 patients with 14601 clinical visits between 1999-2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL) levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF). RESULTS:Most patients (n = 495; 57.0%) switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2%) or without drug resistance mutations (DRM) (n = 250; 28.8%) experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90-3.96) and 3.20 (95% 2.65-3.75), respectively) compared with those who switched without VF (4.53 years). Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART. CONCLUSIONS:In the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.