Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals.

Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

Morbidity and Length of Stay After Injury Among People Experiencing Homelessness in North America.

Importance: Traumatic injury is a leading cause of hospitalization among people experiencing homelessness. However, hospital course among this population is unknown. Objective: To evaluate whether homelessness was associated with increased morbidity and length of stay (LOS) after hospitalization for traumatic injury and whether associations between homelessness and LOS were moderated by age and/or Injury Severity Score (ISS). Design, Setting, and Participants: This retrospective cohort study of the American College of Surgeons Trauma Quality Programs (TQP) included patients 18 years or older who were hospitalized after an injury and discharged alive from 787 hospitals in North America from January 1, 2017, to December 31, 2018. People experiencing homelessness were propensity matched to housed patients for hospital, sex, insurance type, comorbidity, injury mechanism type, injury body region, and Glasgow Coma Scale score. Data were analyzed from February 1, 2022, to May 31, 2023. Exposures: People experiencing homelessness were identified using the TQP's alternate home residence variable. Main Outcomes and Measures: Morbidity, hemorrhage control surgery, and intensive care unit (ICU) admission were assessed. Associations between homelessness and LOS (in days) were tested with hierarchical multivariable negative bionomial regression. Moderation effects of age and ISS on the association between homelessness and LOS were evaluated with interaction terms. Results: Of 1 441 982 patients (mean [SD] age, 55.1 [21.1] years; (822 491 [57.0%] men, 619 337 [43.0%] women, and 154 [0.01%] missing), 9065 (0.6%) were people experiencing homelessness. Unmatched people experiencing homelessness demonstrated higher rates of morbidity (221 [2.4%] vs 25 134 [1.8%]; P < .001), hemorrhage control surgery (289 [3.2%] vs 20 331 [1.4%]; P < .001), and ICU admission (2353 [26.0%] vs 307 714 [21.5%]; P < .001) compared with housed patients. The matched cohort comprised 8665 pairs at 378 hospitals. Differences in rates of morbidity, hemorrhage control surgery, and ICU admission between people experiencing homelessness and matched housed patients were not statistically significant. The median unadjusted LOS was 5 (IQR, 3-10) days among people experiencing homelessness and 4 (IQR, 2-8) days among matched housed patients (P < .001). People experiencing homelessness experienced a 22.1% longer adjusted LOS (incident rate ratio [IRR], 1.22 [95% CI, 1.19-1.25]). The greatest increase in adjusted LOS was observed among people experiencing homelessness who were 65 years or older (IRR, 1.42 [95% CI, 1.32-1.54]). People experiencing homelessness with minor injury (ISS, 1-8) had the greatest relative increase in adjusted LOS (IRR, 1.30 [95% CI, 1.25-1.35]) compared with people experiencing homelessness with severe injury (ISS ≥16; IRR, 1.14 [95% CI, 1.09-1.20]). Conclusions and Relevance: The findings of this cohort study suggest that challenges in providing safe discharge to people experiencing homelessness after injury may lead to prolonged LOS. These findings underscore the need to reduce disparities in trauma outcomes and improve hospital resource use among people experiencing homelessness.

Emergency department use after outpatient thyroidectomy across three states.

BACKGROUND: Although outpatient thyroidectomy has become common, few large-scale studies have examined post-thyroidectomy emergency department use, readmission, and encounters not resulting in readmission, known as "treat-and-release" encounters. We evaluated post-outpatient thyroidectomy emergency department use and readmission and characterized associated factors. METHODS: Using the Healthcare Cost and Utilization Project databases, we identified adult outpatient (same-day or <24-hour discharge) thyroidectomies performed in Florida, Maryland, and New York from 2016 to 2017. We identified the procedures linked with emergency department treat-and-release encounters and readmissions within 30 days postoperatively and the factors associated with post-thyroidectomy emergency department use and readmission. RESULTS: Of the 17,046 patients who underwent outpatient thyroidectomy at 374 facilities, 7.5% had emergency department treat-and-release encounters and 2.3% readmissions. The most common reasons for emergency department treat-and-release encounters (9.9%) and readmissions (22.2%) were hypocalcemia-related diagnoses. Greater odds of treat-and-release were associated with identifying as non-Hispanic Black (adjusted odds ratio: 1.5, 95% confidence interval: 1.3-1.8) or Hispanic race/ethnicity (adjusted odds ratio: 1.4, 95% CI: 1.1-1.6), having Medicaid insurance (adjusted odds ratio: 2.7, 95% CI: 2.3-3.2), and living in non-metropolitan areas (adjusted odds ratio: 1.6, 95% CI: 1.1-2.2). We observed no associations between these factors and the odds of readmission. CONCLUSION: Emergency department use after outpatient thyroidectomy is common. Racial, ethnic, socioeconomic, and geographic disparities are associated with treat-and-release encounters but not readmissions. Standardization of perioperative care pathways, focusing on identifying and addressing specific issues in vulnerable populations, could improve care, reduce disparities, and improve patient experience by avoiding unnecessary emergency department visits after outpatient thyroidectomy.

Does Trauma Center Volume Account for the Association Between Trauma Center Verification Level and In-Hospital Mortality among Children Injured by Firearms in California?

BACKGROUND: Heterogeneity in trauma center designation and injury volume offer possible explanations for inconsistencies in pediatric trauma center designation's association with lower mortality among children. We hypothesized that rigorous trauma center verification, regardless of volume, would be associated with lower firearm injury-associated mortality in children. STUDY DESIGN: This retrospective cohort study leveraged the California Office of Statewide Health Planning and Development patient discharge data. Data from children aged 0 to 14 years in California from 2005 to 2018 directly transported with firearm injuries were analyzed. American College of Surgeons (ACS) trauma center verification level was the primary predictor of in-hospital mortality. Centers' annual firearm injury volume data were analyzed as a mediator of the association between center verification level and in-hospital mortality. Two mixed-effects multivariable logistic regressions modeled in-hospital mortality and the estimated association with center verification while adjusting for patient demographic and clinical characteristics. One model included the center's firearm injury volume and one did not. RESULTS: The cohort included 2,409 children with a mortality rate of 8.6% (n = 206). Adjusted odds of mortality were lower for children at adult level I (adjusted odds ratio [aOR] 0.38, 95% CI 0.19 to 0.80), pediatric (aOR 0.17, 95% CI 0.05 to 0.61), and dual (aOR 0.48, 95% CI 0.25 to 0.93) trauma centers compared to nontrauma/level III/IV centers. Firearm injury volume did not mediate the association between ACS trauma center verification and mortality (aOR/10 patient increase in volume 1.01, 95% CI 0.99 to 1.03). CONCLUSIONS: Trauma center verification level, regardless of firearm injury volume, was associated with lower firearm injury-associated mortality, suggesting that the ACS verification process is contributing to achieving optimal outcomes.

Relationship Between Residents' Physiological Stress and Faculty Leadership Skills in a Department of Surgery.

BACKGROUND: Leadership skills of team leaders can impact the functioning of their teams. It is unknown whether attending surgeons' leadership skills impact residents' physiological stress. This study sought to (1) assess the relationship between attending surgeons' leadership skills and residents' physiological stress and (2) to characterize lifestyle behaviors associated with resident physiological stress. We hypothesized that strong attending leadership skills would be associated with low resident physiological stress. STUDY DESIGN: This prospective observational cohort study was conducted at a single urban, academic medical center in the US, over 12 months. Residents were enrolled during their rotation of 1 to 2 months on the Trauma and ICU services. The primary predictor was the attending surgeons' leadership skills that were measured using a weekly survey filled out by residents, using the Surgeons' Leadership Inventory (SLI). The SLI uses a 4-point Likert scale to measure surgeons' leadership skills across eight domains. The primary outcome was residents' physiological stress, which was measured by their Heart Rate Variability (HRV). We recorded the residents' HRV with a WHOOP strap that was continuously worn on the wrist or the bicep. We used multivariate repeated measures gamma regression to assess the relationship between attending leadership skills and residents' physiological stress, adjusting for hours of sleep, age, and service. RESULTS: Sixteen residents were enrolled over 12 months. The median attending surgeons' leadership score was 3.8 (IQR: 3.2-4.0). The median residents' percent of maximal HRV was 70.8% (IQR: 56.7-83.7). Repeated measure gamma regression model demonstrated a minimal nonsignificant increase of 1.6 % (95% CI: -5.6, 8.9; p-value = 0.65) in the percent of maximal HRV (less resident physiological stress) for every unit increase in leadership score. There was an increase of 2.9% (95% CI= 1.6, 4.2; p-value < 0.001) in the percent of maximal HRV per hour increase in sleep and a significant decrease of 10.9% (95% CI= -16.8, -5.2; < 0.001) in the percent of HRV when working in the ICU compared to the Trauma service. CONCLUSION: This study revealed that more residents' sleep was associated with lower physiological stress. Attending surgeons' leadership skills were not associated with residents' physiological stress.

Injury Patterns and Hospital Admission After Trauma Among People Experiencing Homelessness.

Importance: Traumatic injury is a major cause of morbidity for people experiencing homelessness (PEH). However, injury patterns and subsequent hospitalization among PEH have not been studied on a national scale. Objective: To evaluate whether differences in mechanisms of injury exist between PEH and housed trauma patients in North America and whether the lack of housing is associated with increased adjusted odds of hospital admission. Design, Setting, and Participants: This was a retrospective observational cohort study of participants in the 2017 to 2018 American College of Surgeons' Trauma Quality Improvement Program. Hospitals across the US and Canada were queried. Participants were patients aged 18 years or older presenting to an emergency department after injury. Data were analyzed from December 2021 to November 2022. Exposures: PEH were identified using the Trauma Quality Improvement Program's alternate home residence variable. Main Outcomes and Measures: The primary outcome was hospital admission. Subgroup analysis was used to compared PEH with low-income housed patients (defined by Medicaid enrollment). Results: A total of 1 738 992 patients (mean [SD] age, 53.6 [21.2] years; 712 120 [41.0%] female; 97 910 [5.9%] Hispanic, 227 638 [13.7%] non-Hispanic Black, and 1 157 950 [69.6%] non-Hispanic White) presented to 790 hospitals with trauma, including 12 266 PEH (0.7%) and 1 726 726 housed patients (99.3%). Compared with housed patients, PEH were younger (mean [SD] age, 45.2 [13.6] years vs 53.7 [21.3] years), more often male (10 343 patients [84.3%] vs 1 016 310 patients [58.9%]), and had higher rates of behavioral comorbidity (2884 patients [23.5%] vs 191 425 patients [11.1%]). PEH sustained different injury patterns, including higher proportions of injuries due to assault (4417 patients [36.0%] vs 165 666 patients [9.6%]), pedestrian-strike (1891 patients [15.4%] vs 55 533 patients [3.2%]), and head injury (8041 patients [65.6%] vs 851 823 patients [49.3%]), compared with housed patients. On multivariable analysis, PEH experienced increased adjusted odds of hospitalization (adjusted odds ratio [aOR], 1.33; 95% CI, 1.24-1.43) compared with housed patients. The association of lacking housing with hospital admission persisted on subgroup comparison of PEH with low-income housed patients (aOR, 1.10; 95% CI, 1.03-1.19). Conclusions and Relevance: Injured PEH had significantly greater adjusted odds of hospital admission. These findings suggest that tailored programs for PEH are needed to prevent their injury patterns and facilitate safe discharge after injury.

Re-triage moderates association between state trauma funding and lower mortality of trauma patients.

BACKGROUND: Severely injured patients who are re-triaged (emergently transferred from an emergency department to a high-level trauma center) experience lower in-hospital mortality. Patients in states with trauma funding also experience lower in-hospital mortality. This study examines the interaction of re-triage, state trauma funding, and in-hospital mortality. STUDY DESIGN: Severely injured patients (Injury Severity Score (ISS) >15) were identified from 2016 to 2017 Healthcare Cost and Utilization Project State Emergency Department Databases and State Inpatient Databases in five states (FL, MA, MD, NY, WI). Data were merged with the American Hospital Association Annual Survey and state trauma funding data. Patients were linked across hospital encounters to determine if they were appropriately field triaged, field under-triaged, optimally re-triaged, or sub-optimally re-triaged. A hierarchical logistic regression modeling in-hospital mortality was used to quantify the effect of re-triage on the association between state trauma funding and in-hospital mortality, while adjusting for patient and hospital characteristics. RESULTS: A total of 241,756 severely injured patients were identified. Median age was 52 years (IQR: 28, 73) and median ISS was 17 (IQR: 16, 25). Two states (MA, NY) allocated no funding, while three states (WI, FL, MD) allocated $0.09-$1.80 per capita. Patients in states with trauma funding were more broadly distributed across trauma center levels, with a higher proportion of patients brought to Level III, IV, or non-trauma centers, compared to patients in states without trauma funding (54.0% vs. 41.1%, p < 0.001). Patients in states with trauma funding were more often re-triaged, compared to patients in states without trauma funding (3.7% vs. 1.8%, p < 0.001). Patients who were optimally re-triaged in states with trauma funding experienced 0.67 lower adjusted odds of in-hospital mortality (95% CI: 0.50-0.89), compared to patients in states without trauma funding. We found that re-triage significantly moderated the association between state trauma funding and lower in-hospital mortality (p = 0.018). CONCLUSION: Severely injured patients in states with trauma funding are more often re-triaged and experience lower odds of mortality. Re-triage of severely injured patients may potentiate the mortality benefit of increased state trauma funding.

Hospital variability in adoption of alcohol and drug screening in adult trauma patients.

BACKGROUND: Despite recommendations to screen all injured patients for substance use, single-center studies have reported underscreening. This study sought to determine if there was significant practice variability in adoption of alcohol and drug screening of injured patients among hospitals participating in the Trauma Quality Improvement Program. METHODS: This was a retrospective observational cross-sectional study of trauma patients 18 years or older in Trauma Quality Improvement Program 2017-2018. Hierarchical multivariable logistic regression modeled the odds of screening for alcohol and drugs via blood/urine test while controlling for patient and hospital variables. We identified statistically significant high and low-screening hospitals based on hospitals' estimated random intercepts and associated confidence intervals (CIs). RESULTS: Of 1,282,111 patients at 744 hospitals, 619,423 (48.3%) were screened for alcohol, and 388,732 (30.3%) were screened for drugs. Hospital-level alcohol screening rates ranged from 0.8% to 99.7%, with a mean rate of 42.4% (SD, 25.1%). Hospital-level drug screening rates ranged from 0.2% to 99.9% (mean, 27.1%; SD, 20.2%). A total of 37.1% (95% CI, 34.7-39.6%) of variance in alcohol screening and 31.5% (95% CI, 29.2-33.9%) of variance in drug screening were at the hospital level. Level I/II trauma centers had higher adjusted odds of alcohol screening (adjusted odds ratio [aOR], 1.31; 95% CI, 1.22-1.41) and drug screening (aOR, 1.16; 95% CI, 1.08-1.25) than Level III and nontrauma centers. We found 297 low-screening and 307 high-screening hospitals in alcohol after adjusting for patient and hospital variables. There were 298 low-screening and 298 high-screening hospitals for drugs. CONCLUSION: Overall rates of recommended alcohol and drug screening of injured patients were low and varied significantly between hospitals. These results underscore an important opportunity to improve the care of injured patients and reduce rates of substance use and trauma recidivism. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

How does Injury Severity Score derived from International Classification of Diseases Programs for Injury Categorization using International Classification of Diseases, Tenth Revision, Clinical Modification codes perform compared with Injury Severity Score derived from Trauma Quality Improvement Program?

BACKGROUND: Injury Severity Score (ISS) is a measurement of injury severity based on the Abbreviated Injury Scale. Because of the difficulty and expense of Abbreviated Injury Scale coding, there have been recent efforts in mapping ISS from administrative International Classification of Diseases ( ICD ) codes instead. Specifically, the open source and freely available International Classification of Diseases Programs for Injury Categorization (ICDPIC) in R (Foundation for Statistical Computing, Vienna, Austria) converts International Classification of Diseases, Ninth Revision, codes to ISS. This study aims to compare ICDPIC calculations versus manually derived Trauma Quality Improvement Program (TQIP) calculations for International Classification of Diseases, Tenth Revision ( ICD-10 ), codes. Moderate concordance was chosen as the hypothetical relationship because of previous work by both Fleischman et al. ( J Trauma Nurs. 2017;24(1):4-14) who found moderate to substantial concordance between ICDPIC and ISS and Di Bartolomeo et al. ( Scand J Trauma Resusc Emerg Med. 2010;18(1):17) who found none to slight concordance. Given these very different findings, we thought it reasonable to predict moderate concordance with the use of more detailed ICD-10 codes. METHODS: This was an observational cohort study of 1,040,728 encounters in the TQIP registry for the year 2018. International Classification of Diseases Programs for Injury Categorization in R was used to derive ISS from the ICD-10 codes in the registry. The resulting scores were compared with the manually derived ISS in TQIP. RESULTS: The median difference between ISS calculated by ICDPIC-2021 using ICD-10, Clinical Modification (ISS-ICDPIC), and manually derived ISS was -3 (95% confidence interval, -5 to 0), while the mean difference was -2.09 (95% confidence interval, -2.10 to -2.07). There was substantial concordance between ISS-ICDPIC and manually derived ISS ( κ = 0.66). The ISS-ICDPIC was a better predictor of mortality (area under the curve, 0.853 vs. 0.836) but a worse predictor of intensive care unit admission (area under the curve, 0.741 vs. 0.757) and hospital stay ≥10 days (AUC, 0.701 vs. 0.743). The ICDPIC has substantial concordance with TQIP for the firearm ( κ = 0.69), motor vehicle trauma ( κ = 0.71), and pedestrian ( κ = 0.73) injury mechanisms. CONCLUSION: When TQIP data are unavailable, ICDPIC remains a valid way to calculate ISS after transition to ICD-10 codes. The ISS-ICDPIC performs well in predicting a number of outcomes of interest but is best served as a predictor of mortality. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Sex-Based Disparities in Timeliness of Trauma Care and Discharge Disposition.

Importance: Differences in time to diagnostic and therapeutic measures can contribute to disparities in outcomes. However, whether there is an association of timeliness by sex for trauma patients is unknown. Objective: To investigate whether sex-based differences in time to definitive interventions exist for trauma patients in the US and whether these differences are associated with outcomes. Design, Setting, and Participants: This was a retrospective cohort study conducted from July 2020 to July 2021, using the 2013 to 2016 Trauma Quality Improvement Program (TQIP) databases from level I to III trauma centers in the US. Patients 18 years or older with an Injury Severity Score (ISS) greater than 15 and who carried diagnoses of traumatic brain injury, intra-abdominal injury, pelvic fracture, femur fracture, and spinal injury as a result of their trauma were included in the study. Data were analyzed from July 2020 to July 2021. Main Outcomes and Measures: Primary outcomes assessed timeliness to interventions, using Wilcoxon signed rank and χ2 tests. Secondary outcomes included location of discharge after injury, using propensity score-matched generalized estimating equations modeling. Results: Of the 28 332 patients included, 20 002 (70.6%) were male patients (mean [SD] age, 43.3 [18.2] years) and 8330 (29.4%) were female patients (mean [SD] age, 48.5 [21.1] years), with significantly different distributions of ISS scores (ISS score 16-24: male patient, 10 622 [53.1%]; female patient, 4684 [56.2%]; ISS score 41-74: male patient, 2052 [10.3%]; female patient, 852 [10.2%]). Male patients more frequently had abdominal (4257 [21.3%] vs 1268 [15.2%]) and spinal cord (3989 [20.0%] vs 1274 [15.3%]) injuries, whereas female patients experienced greater proportions of femur (3670 [44.0%] vs 8422 [42.1%]) and pelvic (3970 [47.6%] vs 6963 [34.8%]) fractures. Female patients experienced significantly longer emergency department length of stay (median [IQR], 184 [92-314] minutes vs 172 [86-289] minutes; P < .001), longer time in pretriage (median [IQR], 52 [36-80] minutes vs 49 [34-77] minutes; P < .001), and increased likelihood of discharge to nursing or long-term care facilities instead of home after matching by age, ISS, mechanism, and injury type (male patient:female patient, odds ratio, 0.72; 95% CI, 0.67-0.78). Conclusions and Relevance: Results of this cohort study suggest that female trauma patients experienced slightly longer delays in trauma care and had a higher likelihood of discharge to long-term care facilities than their male counterparts.

Characteristics and Specialist Linkage to Care of Patients Diagnosed With Chronic Hepatitis C Across Different Settings in an Urban Academic Hospital: Implications for Improving Diagnosis and Linkage to Care.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is a significant public health problem. Strategies to identify more HCV infections and improve linkage to care (LTC) are needed. We compared characteristics, treatment and LTC among chronic HCV patients in different health care settings. METHODS: Newly diagnosed HCV antibody positive (anti-HCV+) patients within settings of acute care, inpatient and outpatient in one health system were studied. Proportion of LTC and treatment were analyzed only for HCV RNA positive patients. Chi-square, one-way ANOVA and logistic regression were used to compare the characteristics and outcomes in the three care settings. Patients in acute care settings were excluded from multivariate analyses due to low sample size. RESULTS: About 43, 368, and 1159 anti-HCV+ individuals were identified in acute care, inpatient, and outpatient, respectively. Proportion of RNA positivity in acute, inpatient, and outpatient were 47.8, 60.3 and 29.2%, respectively (p < 0.01). After adjusting for age, insurance type, race, and gender, outpatients had higher odds of LTC and of treatment (OR 4.7 [2.9, 7.6] and 4.5 [2.8, 7.3]). CONCLUSIONS: Inpatients had lower proportion of LTC and treatment compared to outpatients. Use of LTC coordinators and the provision of integrated service for specialty care may improve outcomes.

Patterns of repeated anal cytology results among HIV-positive and HIV-negative men who have sex with men.

BACKGROUND: Men who have sex with men (MSM) are at increased risk for anal cancer. In cervical cancer screening, patterns of repeated cytology results are used to identify low- and high-risk women, but little is known about these patterns for anal cytology among MSM. METHODS: We analyzed Multicenter AIDS Cohort Study (MACS) data for MSM who were offered anal cytology testing annually (HIV-positive) or every 2 years (HIV-negative) for 4 years. RESULTS: Following an initial negative (normal) cytology, the frequency of a second negative cytology was lower among HIV-positive MSM with CD4 ≥ 500 (74%) or CD4 < 500 (68%) than HIV-negative MSM (83%) (p < 0.001). After an initial abnormal cytology, the frequency of a second abnormal cytology was highest among HIV-positive MSM with CD4 < 500 (70%) compared to CD4 ≥ 500 (53%) or HIV-negative MSM (46%) (p = 0.003). Among HIV-positive MSM with at least three results, 37% had 3 consecutive negative results; 3 consecutive abnormal results were more frequent among CD4 < 500 (22%) than CD4 ≥ 500 (10%) (p = 0.008). CONCLUSIONS: More than one-third of HIV-positive MSM have consistently negative anal cytology over three years. Following abnormal anal cytology, a repeated cytology is commonly negative in HIV-negative or immunocompetent HIV-positive men, while persistent cytological abnormality is more likely among HIV-positive men with CD4 < 500.

Changes in bone turnover markers with HIV seroconversion and ART initiation.

Background: Osteoporosis is common among HIV-infected persons and contributes to risk of fragility fracture. While ART initiation is associated with decreases in bone mineral density and increases in bone turnover, the impact of HIV on bone metabolism is unclear. Methods: We identified men at the Chicago site of the Multicenter AIDS Cohort Study who HIV seroconverted while under observation. Concentrations of 25-OH vitamin D, bone turnover markers [procollagen type 1 N terminal propeptide (P1NP), osteocalcin (OC), C-telopeptide (CTX)] and sclerostin were measured from stored serum obtained at pre-HIV infection, pre-ART and post-ART initiation timepoints. Mixed models, with each biomarker as an outcome, were fitted. Timepoint, age, CD4 count (cells/mm 3 ), HIV-viral suppression, season and an age by timepoint interaction term were considered as fixed effects. Results: Data from 52 participants revealed that median duration between HIV seroconversion and ART initiation was 8.7 years (IQR 3.7-11.6). Median CD4 and plasma HIV-RNA concentrations were 445 (IQR 298.5-689) and 20 184 copies/mL (IQR 6237-64 340), respectively, at the pre-ART timepoint. Multivariate analyses demonstrated pre-HIV infection levels of OC that were higher than pre-ART levels (6.8 versus 5.7 ng/mL, P = 0.04); and pre-ART levels of sclerostin that were higher than post-ART levels (0.033 versus 0.02 ng/mL, P <0.001). No changes in P1NP, CTX and 25-OH vitamin D levels were detected. Conclusions: HIV seroconversion was associated with decreased OC levels while ART initiation was associated with decreases in sclerostin, a negative regulator of bone formation. Our results suggest that both HIV infection and ART have an impact on bone metabolism in white men.

The association of medication use with clearance or persistence of oral HPV infection.

PURPOSE: Persistent oral human papillomavirus (HPV) infection increases risk for oropharyngeal carcinoma, and people living with HIV have higher rates of oral HPV infection and related cancers. Some prescription medications have immunomodulatory effects, but the impact of medication use on oral HPV natural history is unknown. METHODS: Scope® oral rinse-and-gargle samples were collected semi-annually from 1,666 participants and tested for 37 types of oral HPV DNA using PCR; 594 HPV-infected participants with 1,358 type-specific oral HPV infections were identified. Data were collected on recent (past 6 months) use of medications. The relationship between medication use and oral HPV clearance was evaluated using Wei-Lin-Weissfeld regression, adjusting for biologic sex, prevalent versus incident infection, age, HIV status and CD4+ T cell count. RESULTS: Out of 11 medications examined, oral HPV clearance was significantly reduced in participants reporting recent use of antipsychotics (HR 0.75, 95% CI 0.57-0.99), anxiolytics/sedatives (HR 0.78, 95% CI 0.63-0.96) and antidepressants (HR 0.82, 95% CI 0.67-0.999). Among antipsychotics users, effect modification by HIV status was observed, with reduced clearance in HIV-infected (HR 0.67, 95% CI 0.49-0.91), but not HIV-uninfected participants (p-interaction = 0.009). After adjusted analysis, antipsychotic use remained significantly associated with reduced oral HPV clearance overall (aHR 0.75, 95% CI 0.57-0.99), and when restricted to only HIV-infected participants (aHR 0.66, 95% CI 0.48-0.90). After adjustment, anxiolytic/sedative use and antidepressant use were no longer significantly associated with reduced oral HPV clearance. CONCLUSIONS: Some medications were associated with decreased oral HPV clearance, most notably antipsychotic medications. These medications are prescribed for conditions that may have immunomodulating effects, so characteristics of underlying illness may have partially contributed to reduced oral HPV clearance.

Determining Survey Satisficing of Online Longitudinal Survey Data in the Multicenter AIDS Cohort Study: A Group-Based Trajectory Analysis.

BACKGROUND: Survey satisficing occurs when participants respond to survey questions rapidly without carefully reading or comprehending them. Studies have demonstrated the occurrence of survey satisficing, which can degrade survey quality, particularly in longitudinal studies. OBJECTIVE: The aim of this study is to use a group-based trajectory analysis method to identify satisficers when similar survey questions were asked periodically in a long-standing cohort, and to examine factors associated with satisficing in the surveys having sensitive human immunodeficiency virus (HIV)-related behavioral questions. METHODS: Behavioral data were collected semiannually online at all four sites of the Multicenter AIDS Cohort Study (MACS) from October 2008 through March 2013. Based on the start and end times, and the word counts per variable, response speed (word counts per second) for each participant visit was calculated. Two-step group-based trajectory analyses of the response speed across 9 study visits were performed to identify potential survey satisficing. Generalized linear models with repeated measures were used to investigate the factors associated with satisficing on HIV-related behavioral surveys. RESULTS: Among the total 2138 male participants, the median baseline age was 51 years (interquartile range, 45-58); most of the participants were non-Hispanic white (62.72%, 1341/2138) and college graduates (46.59%, 996/2138), and half were HIV seropositive (50.00%, 1069/2138). A total of 543 men (25.40%, 543/2138) were considered potential satisficers with respect to their increased trajectory tendency of response speed. In the multivariate analysis, being 10 years older at the baseline visit increased the odds of satisficing by 44% (OR 1.44, 95% CI 1.27-1.62, P<.001). Compared with the non-Hispanic white participants, non-Hispanic black participants were 122% more likely to satisfice the HIV-related behavioral survey (OR 2.22, 95% CI 1.69-2.91, P<.001), and 99% more likely to do so for the other race/ethnicity group (OR 1.99, 95% CI 1.39-2.83, P<.001). Participants with a high school degree or less were 67% more likely to satisfice the survey (OR 1.67, 95% CI 1.26-2.21, P<.001) compared with those with a college degree. Having more than one sex partner and using more than one recreational drug reduced the odds of satisficing by 24% (OR 0.76, 95% CI 0.61-0.94, P=.013) and 28% (OR 0.72, 95% CI 0.55-0.93, P=.013), respectively. No statistically significant association of HIV serostatus with satisficing was observed. CONCLUSIONS: Using a group-based trajectory analysis method, we could identify consistent satisficing on HIV-related behavioral surveys among participants in the MACS, which was associated with being older, being non-white, and having a lower education level; however, there was no significant difference by HIV serostatus. Methods to minimize satisficing using longitudinal survey data are warranted.

Human Papillomavirus (HPV) 16 E6 seropositivity is elevated in subjects with oral HPV16 infection.

INTRODUCTION: Human Papillomavirus (HPV) 16 E6 serum antibodies are common in people with HPV-related oropharyngeal cancers (HPV-OPC), but not the general population. We explored HPV16 seroprevalence in people with and without oral HPV16 infection, the cause of HPV-OPC. METHODS: Oral rinse samples were collected semiannually and tested for 36 types of HPV DNA by PCR. HPV16 E6 serum antibodies were tested at the visit of first oral HPV detection in participants with prevalent (n=54), or incident (n=39) oral HPV16 DNA; or at baseline in matched participants with no oral HPV16 DNA (n=155) using multiplex serology assay. Predictors of seropositivity were examined using logistic regression. RESULTS: HPV16 E6 seropositivity (7.5% vs 0.7%; p=0.005) but not seropositivity to the other HPV16 antigens, was significantly more common in those with than without oral HPV16 infection. There were only 8 HPV16 E6 seropositive participants, but oral HPV16 DNA remained a strong predictor of E6 seropositivity after adjustment for other risk factors (aOR=14.6 95%CI, 1.7-122.5). Seroprevalence was similar in those with prevalent (7.4%; 4/54), and incident (7.7%; 3/39) oral HPV16 infection (p=1.00). E6 seroprevalence was associated with reduced oral HPV16 clearance, but was not statistically significant (HR=0.65 95% CI, 0.16-2.70). Seropositive participants were primarily male (87.5%), HIV-positive (75.0%; median CD4 cell-count of 840) and had oral HPV16 DNA (87.5%). History of an HPV-related cancer (0/8) or HPV-related anogenital dysplasia (1/8) was rare, and 4 participants had recent screening showing no anogenital dysplasia. DISCUSSION: HPV16 E6 seropositivity was higher among people with than without oral HPV16 infection, despite no known anogenital disease in these participants.

Association of serum cytokines with oral HPV clearance.

BACKGROUND: Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored. METHODS: From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1ß, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count. RESULTS: Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95% CI=0.34-0.79) and women (aHR=0.76, 95% confidence interval [CI]=0.55-1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50-0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4⩾500 or CD4<500 cells/µl) among HIV-infected participants. No other cytokines were associated with clearance. CONCLUSION: High serum TNF-α is associated with reduced clearance of oral HPV infection.

Anal Cancer Screening in Men Who Have Sex With Men in the Multicenter AIDS Cohort Study.

OBJECTIVE: To evaluate the prevalence of anal cytology (ACyt) abnormalities among HIV-infected and HIV-uninfected men who have sex with men (MSM). DESIGN: Multicenter cohort study of 723 HIV-infected and 788 HIV-uninfected MSM with ACyt, with a second ACyt collected 2 years later. A referral for high-resolution anoscopy was suggested for abnormal ACyt. METHODS: ACyt samples were collected using a polyester swab and liquid cytology media and read in a central laboratory. RESULTS: Prevalence of any abnormal ACyt was 25% in HIV-uninfected MSM and increased to 38%, 41%, and 47% among HIV-infected MSM with current CD4 T-cell counts ≥500, 350-499, and <350 cells/mm (P < 0.001), respectively. Anal HPV16 DNA was also more common in HIV-infected than HIV-uninfected MSM (25% versus 16%, P < 0.001). Abnormal baseline ACyt together with prevalent HPV16 DNA detection was present in only 7% of HIV-uninfected MSM compared to 18% of HIV-infected MSM with current CD4 < 350, P < 0.001. Among HIV-infected men, 56% of the men with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions ASCs-US/LSILs and 81% of men with atypical squamous cells cannot exclude high-grade (ASC-H/)/high-grade squamous intraepithelial lesions (HSIL) had lower grade ACyt findings 18-30 months later ("regressed"). However, 19% of untreated HIV-infected men with ASC-H/HSIL cytology maintained that same grade of cytology in their second test approximately 2 years later, and 15% with ASC-US/LSIL "progressed" to ASC-H/HSIL. Abnormal ACyt had high sensitivity (96%) but low specificity (17%) for biopsy-proven HSIL. CONCLUSIONS: Prevalence of abnormal ACyt remains elevated in HIV-infected men during the current antiretroviral therapy era.

High Oral Human Papillomavirus Type 16 Load Predicts Long-term Persistence in Individuals With or at Risk for HIV Infection.

The association between oral human papillomavirus 16 (HPV16) DNA load and infection clearance was evaluated among 88 individuals with oral HPV16 infection who were identified within a prospective cohort of 1470 HIV-infected and uninfected individuals. Oral rinse specimens were collected semiannually for up to 5 years. The oral HPV16 load at the time of the first positive test result was significantly associated with the time to clearance of infection (continuous P trends <.01). Notably, clearance rates by 24 months were 41% and 94% in the highest and lowest HPV16 load tertiles (P = .03), respectively. High oral HPV16 load warrants consideration as a biomarker for infection persistence, the presumed precursor of HPV16-associated oropharyngeal cancer.

Comparison of Clinical Features, Virulence, and Relapse among Mycobacterium avium Complex Species.

RATIONALE: Traditionally, Mycobacterium avium complex (MAC) has been composed of M. avium and M. intracellulare; however, advances in genetic sequencing have allowed discovery of several novel species. With these discoveries, investigation of differences in risk factors, virulence, and clinical outcomes have emerged. OBJECTIVES: We conducted a retrospective cohort study evaluating all MAC isolates obtained from pulmonary specimens at our institution from 2000 to 2012 and investigated the clinical courses associated with distinct MAC species. METHODS: To classify isolates into distinct species, a multilocus sequence analysis using rpoB and internal transcribed spacer (ITS) as targets was performed. We reviewed patient medical records to analyze clinical characteristics and outcomes for the cohort. MEASUREMENTS AND MAIN RESULTS: Of the isolates from the 448 included patients, 54% were M. avium, 18% were M. intracellulare, and 28% were M. chimaera. Using American Thoracic Society/Infectious Diseases Society of America criteria, patients whose isolates were identified as M. avium (adjusted odds ratio [AOR], 2.14; 95% confidence interval [CI], 1.33-3.44) or M. intracellulare (AOR, 3.12; 95% CI, 1.62-5.99) were more likely to meet criteria for infection than patients with M. chimaera. Patients infected with M. chimaera were more likely to be prescribed an immunosuppressant compared with all other patients (AOR, 2.75; 95% CI, 1.17-6.40). Patients treated for infections with M. avium (AOR, 5.64; 95% CI, 1.51-21.10) and M. chimaera (AOR, 4.47; 95% CI, 1.08-18.53) were more likely to have a clinical relapse/reinfection than those with M. intracellulare. CONCLUSIONS: Our findings suggest that specific MAC species have varying degrees of virulence and classifying MAC isolates into distinct species aids in identifying which patients are at higher risk of clinical relapse/reinfection.