Patient and Hospital Characteristics Associated with Admission Among Patients With Minor Isolated Extremity Firearm Injuries: A Propensity-Matched Analysis.

Objective: To quantify the association between insurance and hospital admission following minor isolated extremity firearm injury. Background: The association between insurance and injury admission has not been examined. Methods: This was an observational retrospective cohort study of minor isolated extremity firearm injury captured in the Healthcare Cost and Utilization Project State Inpatient and Emergency Department Databases in 6 states (New York, Arkansas, Wisconsin, Massachusetts, Florida, and Maryland) from 2016 to 2017 among patients aged 16 years or older. The primary exposure was insurance. Admitted patients were propensity score matched to nonadmitted patients on age, extremity Abbreviated Injury Score, and Elixhauser Comorbidity Index with exact matching within hospital to adjust for selection bias. A general estimating equation logistic regression estimated the association between insurance and odds of admission in the matched cohort while controlling for sex, race, injury intent, injury type, hospital profit type, and trauma center designation with observations clustered by propensity score-matched pairs within hospital. Results: A total of 8151 patients presented to hospital with a minor isolated extremity firearm injury between 2016 and 2017 in 6 states. Patients were 88.0% male, 56.6% Black, and 71.7% aged 16 to 36 years old, and 22.1% were admitted. A total of 2090 patients were matched on propensity for admission. Privately insured matched patients had 1.70 higher adjusted odds of admission and 95% confidence interval of 1.30 to 2.22, compared with uninsured after adjusting for patient and hospital characteristics. Conclusions: Insurance was associated with hospital admission for minor isolated extremity firearm injury.

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.

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.

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.

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.

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.

A longitudinal study of human papillomavirus 16 L1, e6, and e7 seropositivity and oral human papillomavirus 16 infection.

BACKGROUND: Individuals with human papillomavirus (HPV) infections can develop IgG antibodies to HPV proteins including the L1 capsid and E6 and E7 oncoproteins. Evidence on whether L1 antibodies reduce the risk of cervical HPV infection is mixed, but this has not been explored for oral HPV infections. Antibodies to HPV16's E6 oncoprotein have been detected in some oropharyngeal cancer cases years before cancer diagnosis, but it is unknown if these antibodies are associated with oral HPV16 DNA. METHODS: Enzyme-linked immunosorbent assays tested for serum antibodies to HPV16's L1 capsid in 463 HIV-infected and 293 HIV-uninfected adults, and for antibodies to recombinantly expressed E6 and E7 oncoproteins to HPV16 in 195 HIV-infected and 69 HIV-uninfected cancer-free participants at baseline. Oral rinse samples were collected semiannually for up to 3 years and tested for HPV DNA using PGMY 09/11 primers. Adjusted Poisson, logistic, and Wei-Lin-Weissfeld regression models were used. RESULTS: Human papillomavirus 16 L1 seroreactivity did not reduce the subsequent risk of incident oral HPV16 infection in unadjusted (hazard ratio, 1.4; 95% confidence interval, 0.59-3.3) or adjusted (adjusted hazard ratio = 1.1; 95% confidence interval, 0.41-3.0) analysis. Antibodies to HPV16 E6 and E7 oncoproteins were detected in 7.6% and 3.4% of participants, respectively, but they were not associated with baseline oral HPV16 DNA prevalence or oral HPV16 persistence (each P > 0.40). CONCLUSIONS: Naturally acquired HPV16 L1 antibodies did not reduce the risk of subsequent oral HPV16 infection. Human papillomavirus 16 E6 and E7 seropositivity was not a marker for oral HPV16 infection in this population without HPV-related cancer.

Risk factors for acquisition and clearance of oral human papillomavirus infection among HIV-infected and HIV-uninfected adults.

Human papillomavirus (HPV) causes the majority of oropharyngeal cancers in the United States, yet the risk factors for and natural history of oral HPV infection are largely unknown. In 2010-2011, a US-based longitudinal cohort study of 761 human immunodeficiency virus (HIV)-infected and 469 at-risk HIV-uninfected participants from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study was initiated. Semiannually collected oral rinses were evaluated for 37 HPV genotypes using the Roche LINEAR ARRAY HPV Genotyping Test (Roche Molecular Systems, Pleasanton, California), and factors associated with oral HPV incidence and clearance were explored using adjusted Wei-Lin-Weissfeld modeling. Through 2013, the 2-year cumulative incidence of any type of oral HPV infection was 34% in HIV-infected persons and 19% in HIV-uninfected persons. However, many of these infections cleared. Seven percent of incident infections and 35% of prevalent infections persisted for at least 2 years. After adjustment for other risk factors, HIV infection (adjusted hazard ratio = 2.3, 95% confidence interval: 1.7, 3.2), reduced current CD4 cell count, and increased numbers of oral sex and "rimming" partners increased the risk of incident oral HPV infection, whereas male sex, older age, and current smoking increased the risk of oral HPV persistence (each P < 0.05). This helps explain the consistent associations observed between these factors and prevalent oral HPV infection in previous cross-sectional studies.

Risk factors for oral HPV infection among a high prevalence population of HIV-positive and at-risk HIV-negative adults.

INTRODUCTION: Human papillomavirus (HPV) is an important risk factor for oropharyngeal cancer. Individuals with human immunodeficiency virus (HIV) have higher oral HPV prevalence but the risk factors for oral HPV infection are not well understood for either HIV-positive or HIV-negative individuals. METHODS: This study was nested within the Multicenter AIDS Cohort Study (MACS; men) and Women Interagency HIV Study (WIHS; women) cohorts. Exfoliated oral epithelial cells were collected from 379 HIV-positive and 266 at-risk HIV-negative individuals using a rinse and gargle with Scope mouthwash. Samples were tested for 36 types of HPV DNA using PGMY09/11 consensus primers and reverse line blot hybridization. Risk factors for oral HPV infection were explored using logistic regression with generalized estimating equations in this cross-sectional analysis. RESULTS: Prevalent oral HPV infection was common (34%), including HPV16 infection in 5.7% of participants. HIV-positive individuals had increased odds of prevalent oral HPV infection compared with HIV-negative individuals [adjusted OR = 2.1; 95% confidence interval (CI), 1.6-2.8]. Risk factors for prevalent oral HPV differed in HIV-positive and HIV-negative participants. Among HIV-negative individuals, higher number of recent oral sex or rimming partners were strong risk factors for prevalent oral HPV infection (each P(trend) < 0.01). In contrast, among HIV-positive individuals, lower CD4 T-cell count (P(trend) < 0.001) and higher number of lifetime sexual partners (P(trend) = 0.03) were strong risk factors. CONCLUSIONS: Oral HPV prevalence was elevated in HIV-positive individuals after controlling for differences in cigarette smoking and sexual behavior, supporting the possibility that HIV may affect the natural history of oral HPV. IMPACT: Immunosuppression may contribute to increased persistence or progression of oral HPV infection.

A randomized controlled double-masked trial of albuterol add-on therapy in patients with multiple sclerosis.

BACKGROUND: Interleukin 12 (IL-12), a cytokine that promotes generation of helper T cells subtype 1, is increased in multiple sclerosis. Albuterol sulfate, a ß2-adrenergic agonist, reduces IL-12 expression, so we tested the effect of albuterol as an add-on treatment to glatiramer acetate therapy. OBJECTIVES: To investigate the clinical and immunologic effects of albuterol treatment as an add-on therapy in patients starting glatiramer acetate treatment. DESIGN: Single-center double-masked clinical trial. SETTING: Academic research. Patients Subjects with relapsing-remitting multiple sclerosis. MAIN OUTCOME MEASURES: In this single-center double-masked clinical trial, subjects with relapsing-remitting multiple sclerosis were randomized to receive a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of placebo daily for 2 years or a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of albuterol daily for 2 years. The primary clinical efficacy measurement was the change in Multiple Sclerosis Functional Composite at 2 years, and the primary immunologic end point was the change in expression of IL-13 and interferon γ at each study time point. The classification level of evidence from this trial is C for each question, as this is the first class II clinical trial addressing the efficacy of glatiramer acetate plus albuterol. RESULTS: Forty-four subjects were randomized to receive glatiramer acetate plus albuterol or glatiramer acetate plus placebo, and 39 subjects contributed to the analysis. Improvement in the Multiple Sclerosis Functional Composite was observed in the glatiramer acetate plus albuterol group at the 6-month (P = .005) and 12-month (P = .04) time points but not at the 24-month time point. A delay in the time to first relapse was also observed in the glatiramer acetate plus albuterol group (P = .03). Immunologically, IL-13 and interferon-γ production decreased in both treatment groups, and a treatment effect on IL-13 production was observed at the 12-month time point (P < .05). Adverse events were generally mild, and only 3 moderate or severe events were considered related to the treatment. CONCLUSION: Treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00039988.