Marked Reduction of Socioeconomic and Racial Disparities in Invasive Pneumococcal Disease Associated With Conjugate Pneumococcal Vaccines.

BACKGROUND: It is not known whether reductions in socioeconomic and racial disparities in incidence of invasive pneumococcal disease (defined as the isolation of Streptococcus pneumoniae from a normally sterile body site) noted after pneumococcal conjugate vaccine (PCV) introduction have been sustained. METHODS: Individual-level data collected from 20 Tennessee counties participating in Active Bacterial Core surveillance over 19 years were linked to neighborhood-level socioeconomic factors. Incidence rates were analyzed across 3 periods-pre-7-valent PCV (pre-PCV7; 1998-1999), pre-13-valent PCV (pre-PCV13; 2001-2009), and post-PCV13 (2011-2016)-by socioeconomic factors. RESULTS: A total of 8491 cases of invasive pneumococcal disease were identified. Incidence for invasive pneumococcal disease decreased from 22.9 (1998-1999) to 17.9 (2001-2009) to 12.7 (2011-2016) cases per 100 000 person-years. Post-PCV13 incidence (95% confidence interval [CI]) of PCV13-serotype disease in high- and low-poverty neighborhoods was 3.1 (2.7-3.5) and 1.4 (1.0-1.8), respectively, compared with pre-PCV7 incidence of 17.8 (15.7-19.9) and 6.4 (4.9-7.9). Before PCV introduction, incidence (95% CI) of PCV13-serotype disease was higher in blacks than whites (17.3 [15.1-19.5] vs 11.8 [10.6-13.0], respectively); after introduction, PCV13-type disease incidence was greatly reduced in both groups (white: 2.7 [2.4-3.0]; black: 2.2 [1.8-2.6]). CONCLUSIONS: Introduction of PCV13 was associated with substantial reductions in overall incidence and socioeconomic and racial disparities in PCV13-serotype incidence.

Injection Drug Use-Associated Candidemia: Incidence, Clinical Features, and Outcomes, East Tennessee, 2014-2018.

BACKGROUND: Injection drug use (IDU) is an established but uncommon risk factor for candidemia. Surveillance for candidemia is conducted in East Tennessee, an area heavily impacted by the opioid crisis and IDU. We evaluated IDU-associated candidemia to characterize the epidemiology and estimate the burden. METHODS: We assessed the proportion of candidemia cases related to IDU during January 1, 2014-September 30, 2018, estimated candidemia incidence in the overall population and among persons who inject drugs (PWID), and reviewed medical records to compare clinical features and outcomes among IDU-associated and non-IDU candidemia cases. RESULTS: The proportion of IDU-associated candidemia cases in East Tennessee increased from 6.1% in 2014 to 14.5% in 2018. Overall candidemia incidence in East Tennessee was 13.5/100 000, and incidence among PWID was 402-1895/100 000. Injection drug use-associated cases were younger (median age, 34.5 vs 60 years) and more frequently had endocarditis (39% vs 3%). All-cause 30-day mortality was 8% among IDU-associated cases versus 25% among non-IDU cases. CONCLUSIONS: A growing proportion of candidemia in East Tennessee is associated with IDU, posing an additional burden from the opioid crisis. The lower mortality among IDU-associated cases likely reflects in part the younger demographic; however, Candida endocarditis seen among approximately 40% underscores the seriousness of the infection and need for prevention.

Predictors of survival in patients undergoing oropharyngeal surgery for cancer recurrence after radiation therapy.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma continues to rise with the majority of patients receiving definitive or adjunctive radiation. For patients with locoregional recurrence after radiation, optimal treatment involves salvage surgery. The aim of this study is to identify factors that predict survival to ultimately improve patient selection for salvage surgery. METHODS: Retrospective cohort study at an NCI-designated cancer center. We analyzed patients with a history of head and neck radiation who presented with persistent/recurrent or second primary disease requiring salvage oropharyngeal resection from 1998-2017 (n = 120). Patients were stratified into three classes based on time to recurrence and presence of laryngopharyngeal dysfunction. Primary outcomes were 5-year overall survival (OS) and disease specific survival (DSS). RESULTS: Median OS was 27 months (median follow-up 20 months). Five-year OS was 47% for class I (recurrence > 2 years), 26% for class II (recurrence ≤ 2 years), and 0% for class III (recurrence ≤ 2 years and laryngopharyngeal dysfunction), (p < 0.0001). Five-year DSS showed significant differences between classes (p < 0.0001). On multivariate analysis, class remained predictive of OS (p = 0.04- < 0.001) and DSS (p = 0.04-0.001). Adjuvant radiation after salvage surgery with negative margins showed superior OS (71% vs. 28%, p = 0.01) and DSS (83% vs 37%, p = 0.02) compared to surgery alone and was a significant predictor of improved survival on multivariate analysis (HR 0.1, p = 0.04). CONCLUSION: This study identified a subset of patients with oropharyngeal cancer recurrence within two years of initial treatment and with laryngopharyngeal dysfunction who have poor outcomes for salvage surgery.

Intraoperative Fluorescent Angiography Predicts Pharyngocutaneous Fistula After Salvage Laryngectomy.

BACKGROUND: Technology to assess tissue perfusion is exciting with translational potential, although data supporting its clinical applications have been lagging. Patients who have undergone radiation are at particular risk of poor tissue perfusion and would benefit from this expanding technology. We designed a prospective clinical trial using intraoperative indocyanine green angiography to evaluate for wound-healing complications in patients undergoing salvage laryngectomy after radiation failure. PATIENTS AND METHODS: This prospective trial included patients undergoing salvage laryngectomy at a National Cancer Institute-designated tertiary cancer center between 2016 and 2018. After tumor extirpation and prior to reconstruction, 10 mg indocyanine green dye was infused and the fluorescence (FHYPO) and ingress rate of the pharyngeal mucosa recorded. The primary outcome measure was formation of a pharyngocutaneous fistula (PCF). RESULTS: Patients who developed a PCF had significantly lower FHYPO (87 vs 172, p < 0.001) and ingress rates (6.7 vs 15.8, p = 0.043) compared with those who did not develop a fistula. There were no fistulas in patients with FHYPO > 150 (n = 21) or ingress > 15 (n = 15). There was a 50% fistula rate in patients with FHYPO ≤ 103 (n = 10) and ingress rate ≤ 6 (n = 6). CONCLUSIONS: Intraoperative indocyanine green angiography can assess hypoperfusion in patients and predict risk of PCFs after salvage laryngectomy, and can thus intraoperatively risk-stratify patients for postoperative wound-healing complications.

New onset alcohol use disorder following bariatric surgery.

BACKGROUND: Bariatric surgery is the most effective treatment for morbid obesity; however, there may be significant unanticipated psychosocial effects following surgery. Prior studies have identified a threefold increase in the incidence of alcohol use disorder (AUD) after Roux-en-Y gastric bypass (RYGB). With sleeve gastrectomy (SG) now comprising over 50% of primary bariatric operations, the degree to which patients who undergo SG develop AUD remains unknown. We sought to characterize the patients and incidence of AUD following SG compared to RYGB. METHODS: This study used prospectively collected data from a state-wide quality collaborative. The presence of AUD was determined using the Alcohol Use Disorders Identification Test for Consumption (AUDIT-C), with a score ≥ 4 in men and ≥ 3 in women suggestive of AUD. We used bivariate Chi-square tests for categorical variables and independent samples t tests for continuous variables. We used multivariable logistic regression to identify patient characteristics that may predispose patients to development of AUD at 1 and 2 years after surgery. RESULTS: The overall prevalence of AUD in our population (n = 5724) was 9.6% preoperatively, 8.5% at 1 year postoperatively, and 14.0% at 2 years postoperatively. The preoperative, 1-year, and 2-year prevalence of AUD for SG were 10.1%, 9.0%, and 14.4%, respectively. The preoperative, 1-year, and 2-year postoperative prevalence of AUD for RYGB were 7.6%, 6.3%, and 11.9%, respectively. Predisposing patient factors to AUD development included higher educational level (p < 0.01) and higher household income (p < 0.01). CONCLUSIONS: This is first large, multi-institutional study of AUD following SG. The prevalence of alcohol use disorder in patients undergoing SG and RYGB was similar pre- and postoperatively. The majority of patients developed AUD following their second postoperative year. Understanding the timing and incidence of alcohol use disorder in patients undergoing SG-the most commonly performed bariatric operation in the United States-is critical to providing appropriate counseling and treatment.

Workplace injury rates and firm-level turnover in Montana's oil and gas industry.

BACKGROUND: Do workers follow their self-interest by minimizing injury risk in their employment decision? If so, employers could use injury reduction as a recruitment and retention strategy. This study explores whether injury incidence is associated with turnover in Montana's Oil and Gas industry. METHODS: A panel data set of Unemployment Insurance and Workers' Compensation administrative records from 2010 to 2015 was used to model the relationship between turnover and injury claim rates at the firm level. RESULTS: Total turnover and injury rates were found to be positively related while injury rates and separation rates had no such association. Quarters in which the employer experienced a severe injury had a 3.3 percentage point increase in separation rates. DISCUSSION: The findings suggest that injured workers contribute to increased turnover, but coworker turnover does not increase with increased injury rates in the firm. Secondary findings suggest a relationship between recent hires and increased injury rates, although further investigation is required.

Trends in Personal Belief Exemption Rates Among Alternative Private Schools: Waldorf, Montessori, and Holistic Kindergartens in California, 2000-2014.

OBJECTIVES: To evaluate trends in rates of personal belief exemptions (PBEs) to immunization requirements for private kindergartens in California that practice alternative educational methods. METHODS: We used California Department of Public Health data on kindergarten PBE rates from 2000 to 2014 to compare annual average increases in PBE rates between schools. RESULTS: Alternative schools had an average PBE rate of 8.7%, compared with 2.1% among public schools. Waldorf schools had the highest average PBE rate of 45.1%, which was 19 times higher than in public schools (incidence rate ratio = 19.1; 95% confidence interval = 16.4, 22.2). Montessori and holistic schools had the highest average annual increases in PBE rates, slightly higher than Waldorf schools (Montessori: 8.8%; holistic: 7.1%; Waldorf: 3.6%). CONCLUSIONS: Waldorf schools had exceptionally high average PBE rates, and Montessori and holistic schools had higher annual increases in PBE rates. Children in these schools may be at higher risk for spreading vaccine-preventable diseases if trends are not reversed.

Impact of neoadjuvant chemotherapy on surgical outcomes among patients with hormone receptor positive breast cancer.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a surrogate for outcome, but not necessarily conversion to BCT eligibility. We sought to examine the impact of NACT on surgical decision making among HR+ patients. METHODS: Our IRB-approved breast cancer database was queried for patients who underwent NACT, including the clinicopathologic data and surgeon's pre- and post-NACT assessment. Surgical conversion rate (SCR) was defined as patients ineligible for BCT prior to NACT, who were given the choice following NACT. RESULTS: Among 289 patients, pCR rates were highest among patients with HER2-enriched subtype (60%) and lowest in patients with luminal A disease (4%). Overall, the BCT rate was 41%, while 28% opted for bilateral mastectomy across subtypes. Despite a low pCR, the SCR was still high (54%) among patients with the luminal A subtype. CONCLUSION: Despite poor pCR rates, NACT still has potential to improve surgical outcomes among hormone receptor positive patients. The surgical conversion rate is a superior measure of the impact of NACT on surgical decision making than examining BCT rates.

REV1 and polymerase ζ facilitate homologous recombination repair.

REV1 and DNA Polymerase ζ (REV3 and REV7) play important roles in translesion DNA synthesis (TLS) in which DNA replication bypasses blocking lesions. REV1 and Polζ have also been implicated in promoting repair of DNA double-stranded breaks (DSBs). However, the mechanism by which these two TLS polymerases increase tolerance to DSBs is poorly understood. Here we demonstrate that full-length human REV1, REV3 and REV7 interact in vivo (as determined by co-immunoprecipitation studies) and together, promote homologous recombination repair. Cells lacking REV3 were hypersensitive to agents that cause DSBs including the PARP inhibitor, olaparib. REV1, REV3 or REV7-depleted cells displayed increased chromosomal aberrations, residual DSBs and sites of HR repair following exposure to ionizing radiation. Notably, cells depleted of DNA polymerase η (Polη) or the E3 ubiquitin ligase RAD18 were proficient in DSB repair following exposure to IR indicating that Polη-dependent lesion bypass or RAD18-dependent monoubiquitination of PCNA are not necessary to promote REV1 and Polζ-dependent DNA repair. Thus, the REV1/Polζ complex maintains genomic stability by directly participating in DSB repair in addition to the canonical TLS pathway.

Pairing taVNS and CIMT is feasible and may improve upper extremity function in infants.

In this study we combined non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) with 40 h of constraint induced movement therapy (CIMT) in infants. All infants completed the full intervention with no adverse events. Therapists were able to maintain high treatment fidelity and reported high ratings for ease of use and child tolerance. Preliminary results show promising gains on motor outcomes: Mean QUEST increase 19.17 (minimal clinically important difference, MCID 4.89); Mean GMFM increase 13.33 (MCID 1%-3%). Infants also exceeded expectations on Goal Attainment Scores (+1). Early data is promising that taVNS paired with intensive motor CIMT is feasible, reliable, and safe in young infants with hemiplegia, and may help harness activity-dependent plasticity to enhance functional movement.

Presbycusis and Hearing Preservation in Observed Vestibular Schwannomas.

OBJECTIVE: We reviewed a cohort of patients with untreated sporadic vestibular schwannoma (VS) and examined the relationship between high-frequency hearing loss (HFHL) in the non-VS ear and long-term hearing outcomes in the VS-affected ear. We hypothesized that the progression of HFHL is associated with accelerated hearing decline in sporadic VS. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary center. PATIENTS: We studied 102 patients with sporadic VS diagnosed from 1999 to 2015 with ≥5 years of observation (median, 6.92; interquartile range, 5.85-9.29). Sixty-six patients had AAO-HNS class A/B hearing at presentation and were included in analysis. INTERVENTIONS: Audiometry, serial magnetic resonance imaging for observation of VS. MAIN OUTCOME MEASURES: Four-frequency pure tone average (PTA) and word recognition scores (WRS) in the VS-affected ear. Decline in high-frequency PTA (average of thresholds at 4000, 6000, and 8,000 Hz) was defined as ≥10 dB during the study period. Decline in WRS was defined as ≥10%. RESULTS: Compared with those without, patients with progressive HFHL in the non-VS ear were more likely to experience a decline in WRS in the VS ear (80% vs. 54%, p = 0.031). However, the same group showed no difference (52% vs. 41%, p = 0.40) in decline in PTA of the VS ear. CONCLUSIONS: Patients with observed VS who experience progressive HFHL in the non-VS ear are more likely to experience significant declines in speech understanding in the VS-affected ear over time. Patients with a history of presbycusis may have an increased risk of losing serviceable hearing because of sporadic VS.

Syndemic theory and HIV-related risk among young transgender women: the role of multiple, co-occurring health problems and social marginalization.

OBJECTIVES: We assessed whether multiple psychosocial factors are additive in their relationship to sexual risk behavior and self-reported HIV status (i.e., can be characterized as a syndemic) among young transgender women and the relationship of indicators of social marginalization to psychosocial factors. METHODS: Participants (n = 151) were aged 15 to 24 years and lived in Chicago or Los Angeles. We collected data on psychosocial factors (low self-esteem, polysubstance use, victimization related to transgender identity, and intimate partner violence) and social marginalization indicators (history of commercial sex work, homelessness, and incarceration) through an interviewer-administered survey. RESULTS: Syndemic factors were positively and additively related to sexual risk behavior and self-reported HIV infection. In addition, our syndemic index was significantly related to 2 indicators of social marginalization: a history of sex work and previous incarceration. CONCLUSIONS: These findings provide evidence for a syndemic of co-occurring psychosocial and health problems in young transgender women, taking place in a context of social marginalization.

First Report of the Bat Tick Carios kelleyi (Acari: Ixodida: Argasidae) From Vermont, United States.

The soft tick Carios kelleyi (Cooley and Kohls, 1941) is an ectoparasite of bats that can harbor bacteria known to cause disease in humans, such as Rickettsia spp., Bartonella spp., and relapsing fever Borrelia spp. Human-tick encounters may occur when bats occupy attics or similar dwellings with access points to human-inhabited areas. During May 2021, a partially engorged adult female C. kelleyi was collected from a Vermont home with an attic that was being used as a roost by big brown bats, Eptesicus fuscus (Chiroptera: Vespertilionidae). The source of the blood in the tick was the domestic dog, Canis lupus familiaris. Subsequently, eight C. kelleyi larvae were collected from a rescued E. fuscus adult. This is the first report of a soft tick species from Vermont and it is unknown how long C. kelleyi has been present in this state. Reports of C. kelleyi are on the rise across the northeastern United States but the implications for the health of humans, domestic animals, and bats in northern New England remain unclear. Bat management plans should consider the importance of bat exclusion in preventing tick encounters with members of the household and should include a tick monitoring component if bats are evicted.

Comparative hologenomics of two Ixodes scapularis tick populations in New Jersey.

Tick-borne diseases, such as those transmitted by the blacklegged tick Ixodes scapularis, are a significant and growing public health problem in the US. There is mounting evidence that co-occurring non-pathogenic microbes can also impact tick-borne disease transmission. Shotgun metagenome sequencing enables sampling of the complete tick hologenome-the collective genomes of the tick and all of the microbial species contained therein, whether pathogenic, commensal or symbiotic. This approach simultaneously uncovers taxonomic composition and allows the detection of intraspecific genetic variation, making it a useful tool to compare spatial differences across tick populations. We evaluated this approach by comparing hologenome data from two tick samples (N = 6 ticks per location) collected at a relatively fine spatial scale, approximately 23 km apart, within a single US county. Several intriguing variants in the data between the two sites were detected, including polymorphisms in both in the tick's own mitochondrial DNA and that of a rickettsial endosymbiont. The two samples were broadly similar in terms of the microbial species present, including multiple known tick-borne pathogens (Borrelia burgdorferi, Babesia microti, and Anaplasma phagocytophilum), filarial nematodes, and Wolbachia and Babesia species. We assembled the complete genome of the rickettsial endosymbiont (most likely Rickettsia buchneri) from both populations. Our results provide further evidence for the use of shotgun metagenome sequencing as a tool to compare tick hologenomes and differentiate tick populations across localized spatial scales.

Preclinical assessment of clinically streamlined, 3D-printed, biocompatible single- and two-stage tissue scaffolds for ear reconstruction.

Auricular reconstruction is a technically demanding procedure requiring significant surgical expertise, as the current gold standard involves hand carving of the costal cartilage into an auricular framework and re-implantation of the tissue. 3D-printing presents a powerful tool that can reduce technical demands associated with the procedure. Our group compared clinical, radiological, histological, and biomechanical outcomes in single- and two-stage 3D-printed auricular tissue scaffolds in an athymic rodent model. Briefly, an external anatomic envelope of a human auricle was created using DICOM computed tomography (CT) images and modified in design to create a two-stage, lock-in-key base and elevating platform. Single- and two-stage scaffolds were 3D-printed by laser sintering poly-L-caprolactone (PCL) then implanted subcutaneously in five athymic rats each. Rats were monitored for ulcer formation, site infection, and scaffold distortion weekly, and scaffolds were explanted at 8 weeks with analysis using microCT and histologic staining. Nonlinear finite element analysis was performed to determine areas of high strain in relation to ulcer formation. Scaffolds demonstrated precise anatomic appearance and maintenance of integrity of both anterior and posterior auricular surfaces and scaffold projection, with no statistically significant differences in complications noted between the single- and two-staged implantation. While minor superficial ulcers occurred most commonly at the lateral and superior helix coincident with finite element predictions of high skin strains, evidence of robust tissue ingrowth and angiogenesis was visible grossly and histologically. This promising preclinical small animal model supports future initiatives for making clinically viable options for an ear tissue scaffold.

Nosocomial hepatitis A outbreak among healthcare workers and patients in a community hospital during an ongoing statewide outbreak.

OBJECTIVE: The Tennessee Department of Health (TDH) investigated a hepatitis A virus (HAV) outbreak to identify risk factors for infection and make prevention recommendations. DESIGN: Case series. SETTING: Community hospital. PARTICIPANTS: Healthcare workers (HCWs) or patients with laboratory-confirmed acute HAV infection during October 1, 2018-January 10, 2019. METHODS: HCWs with suspected or confirmed hepatitis A infections were interviewed to assess their exposures and activities. Patient medical records and hospital administrative records were reviewed to identify common exposures. We conducted a site investigation to assess knowledge of infection control practices among HCWs. Serum specimens from ill persons were tested for HAV RNA by polymerase chain reaction (PCR) and genotyped. RESULTS: We identified 6 HCWs and 2 patients with laboratory-confirmed HAV infection. All cases likely resulted from exposure to a homeless patient with a history of recreational substance use and undiagnosed HAV infection. Breaches in hand hygiene and use of standard precautions were identified. HAV RNA was detected in 7 serum specimens and all belonged to an identical strain of HAV genotype 1b. CONCLUSIONS: A hepatitis A outbreak among hospital patients and HCWs resulted from exposure to a single patient with undiagnosed HAV infection. Breakdowns in infection control practices contributed to the outbreak. The likelihood of nosocomial transmission can be reduced with proper hand hygiene, standard precautions, and routine disinfection. During community outbreaks, medical providers can better prevent ongoing transmission by including hepatitis A in the differential diagnosis among patients with a history of recreational substance use and homelessness.

Surveillance, Epidemiology, and Estimated Burden of Neonatal Abstinence Syndrome, Tennessee, 2013-2016.

OBJECTIVES: Between 2003 and 2013, the rate of neonatal abstinence syndrome (NAS)-a postnatal drug withdrawal syndrome-in Tennessee increased approximately 10-fold. NAS surveillance is relatively new, and underestimation associated with surveillance has not been described. We compared data from the Tennessee NAS public health surveillance system (TNSS) with a second source of NAS data, hospital discharge data system (HDDS), and estimated the true number of infants with NAS using capture-recapture methods. METHODS: We obtained NAS data on cases of NAS among Tennessee infants from TNSS and HDDS from January 1, 2013, through December 31, 2016. We matched cases of NAS identified in TNSS to cases identified in HDDS. We estimated the true number of infants with NAS by using the Lincoln-Peterson estimator capture-recapture methodology. RESULTS: During the study period, 4070 infants with NAS were reported to TNSS, and 5321 infants with NAS were identified in HDDS; 2757 were in both data sets. Using capture-recapture methods, the total estimated number of infants with NAS during the study period was 7855 (annual mean = 1972; estimated range = 1531-2427), which was 93% more than in TNSS and 48% more than in HDDS. Drugs used for the medication-assisted treatment of substance use disorder were the most commonly reported substances associated with NAS (n = 2389, 59%). CONCLUSIONS: TNSS underestimated the total burden of NAS based on the capture-recapture estimate. Case-based public health surveillance is important for monitoring the burden of and risk factors for NAS and helping guide public health interventions.