Effect of fluoride or chitosan toothpaste and at-home bleaching in enamel roughness, tooth color, and staining susceptibility.

PURPOSE: To evaluate how fluoride- or chitosan-based toothpaste used during at-home bleaching affects enamel roughness, tooth color, and staining susceptibility. METHODS: Bovine enamel blocks were submitted to a 14-day cycling regime considering a factorial design (bleaching agent x toothpaste, 2 x 3), with n=10: (1) bleaching with 16% carbamide peroxide (CP) or 6% hydrogen peroxide (HP), and (2) daily exposure of a fluoride (1,450 ppm F-NaF) toothpaste (FT), chitosan-based toothpaste (CBT), or distilled water (control). Then, 24 hours after the last day of bleaching procedure the samples were exposed to a coffee solution. Color (ΔEab, ΔE00, L*, a*, b*) and roughness (Ra, µm) analyses were performed to compare the samples initially (baseline), after bleaching, and after coffee staining. The results were evaluated by linear models for repeated measures (L*, a*, b*, and Ra), 2-way ANOVA (ΔEab, ΔE00) and Tukey's test (α= 0.05). RESULTS: After the at-home bleaching procedure (toothpaste vs. time, P< 0.0001), the toothpaste groups presented a statistically lower Ra than the control (CBT 0.05). After coffee exposure, CBT presented lower ΔEab and ΔE00 values in the HP groups (toothpaste, P< 0.0001), and lower b* and a* values in the CP groups (toothpaste vs. time, P= 0.004). CLINICAL SIGNIFICANCE: Fluoride or chitosan delivered by toothpaste can reduce surface alterations of the enamel during at-home bleaching, without affecting bleaching efficacy.

Hospital Readmissions Among Persons With Human Immunodeficiency Virus in the United States and Canada, 2005-2018: A Collaboration of Cohort Studies.

BACKGROUND: Hospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005-2018 among adult PWH in NA-ACCORD. METHODS: Linear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (<400 copies/mL), and cohort. RESULTS: We examined 20 189 hospitalizations among 8823 PWH (73% cisgender men, 38% White, 38% Black). PWH hospitalized in 2018 versus 2005 had higher median age (54 vs 44 years), CD4 count (469 vs 274 cells/µL), and virologic suppression (83% vs 49%). Unadjusted 30-day readmissions decreased from 20.1% (95% confidence interval [CI], 17.9%-22.3%) in 2005 to 16.3% (95% CI, 14.1%-18.5%) in 2018. Absolute annual trends were -0.34% (95% CI, -.48% to -.19%) in unadjusted and -0.19% (95% CI, -.35% to -.02%) in adjusted analyses. By index hospitalization reason, there were significant adjusted decreases only for cardiovascular and psychiatric hospitalizations. Readmission reason was most frequently in the same diagnostic category as the index hospitalization. CONCLUSIONS: Readmissions decreased over 2005-2018 but remained higher than the general population's. Significant decreases after adjusting for CD4 count and virologic suppression suggest that factors alongside improved ART contributed to lower readmissions. Efforts are needed to further prevent readmissions in PWH.

Cementum is key to periodontal tissue regeneration: A review on apatite microstructures for creation of novel cementum-based dental implants.

The cementum is the outermost layer of hard tissue covering the dentin within the root portion of the teeth. It is the only hard tissue with a specialized structure and function that forms a part of both the teeth and periodontal tissue. As such, cementum is believed to be critical for periodontal tissue regeneration. In this review, we discuss the function and histological structure of the cementum to promote crystal engineering with a biochemical approach in cementum regenerative medicine. We review the microstructure of enamel and bone while discussing the mechanism underlying apatite crystal formation to infer the morphology of cementum apatite crystals and their complex structure with collagen fibers. Finally, the limitations of the current dental implant treatments in clinical practice are explored from the perspective of periodontal tissue regeneration. We anticipate the possibility of advancing periodontal tissue regenerative medicine via cementum regeneration using a combination of material science and biochemical methods.

Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children.

BACKGROUND: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. METHODS: We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. RESULTS: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78-2.15; P = .32). CONCLUSIONS: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.

Optimizing Treatment for Human Immunodeficiency Virus to Improve Clinical Outcomes Using Precision Medicine.

In first-line antiretroviral therapy (ART) for human immunodeficiency virus (HIV) treatment, some subgroups of patients may respond better to an efavirenz-based regimen than an integrase strand transfer inhibitor (InSTI)-based regimen, or vice versa, due to patient characteristics modifying treatment effects. Using data based on nearly 16,000 patients from the North American AIDS Cohort Collaboration on Research and Design from 2009-2016, statistical methods for precision medicine were employed to estimate an optimal treatment rule that minimizes the 5-year risk of the composite outcome of acquired immune deficiency syndrome (AIDS)-defining illnesses, serious non-AIDS events, and all-cause mortality. The treatment rules considered were functions that recommend either an efavirenz- or InSTI-based regimen conditional on baseline patient characteristics such as demographic information, laboratory results, and health history. The estimated 5-year risk under the estimated optimal treatment rule was 10.0% (95% confidence interval (CI): 8.6, 11.3), corresponding to an absolute risk reduction of 2.3% (95% CI: 0.9, 3.8) when compared with recommending an efavirenz-based regimen for all patients and 2.6% (95% CI: 1.0, 4.2) when compared with recommending an InSTI-based regimen for all. Tailoring ART to individual patient characteristics may reduce 5-year risk of the composite outcome compared with assigning all patients the same drug regimen.

Associations between alcohol and cigarette use and type 1 and 2 myocardial infarction among people with HIV.

OBJECTIVES: People with HIV have a higher risk of myocardial infarction (MI) than the general population, with a greater proportion of type 2 MI (T2MI) due to oxygen demand-supply mismatch compared with type 1 (T1MI) resulting from atherothrombotic plaque disruption. People living with HIV report a greater prevalence of cigarette and alcohol use than do the general population. Alcohol use and smoking as risk factors for MI by type are not well studied among people living with HIV. We examined longitudinal associations between smoking and alcohol use patterns and MI by type among people living with HIV. DESIGN AND METHODS: Using longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort, we conducted time-updated Cox proportional hazards models to determine the impact of smoking and alcohol consumption on adjudicated T1MI and T2MI. RESULTS: Among 13 506 people living with HIV, with a median 4 years of follow-up, we observed 177 T1MI and 141 T2MI. Current smoking was associated with a 60% increase in risk of both T1MI and T2MI. In addition, every cigarette smoked per day was associated with a 4% increase in risk of T1MI, with a suggestive, but not significant, 2% increase for T2MI. Cigarette use had a greater impact on T1MI for men than for women and on T2MI for women than for men. Increasing alcohol use was associated with a lower risk of T1MI but not T2MI. Frequency of heavy episodic alcohol use was not associated with MI. CONCLUSIONS: Our findings reinforce the prioritization of smoking reduction, even without cessation, and cessation among people living with HIV for MI prevention and highlight the different impacts on MI type by gender.

Prevalence and determinants of hepatitis delta virus infection among HIV/hepatitis B-coinfected adults in care in the United States.

Hepatitis delta virus (HDV) infection increases the risk of liver complications compared to hepatitis B virus (HBV) alone, particularly among persons with human immunodeficiency virus (HIV). However, no studies have evaluated the prevalence or determinants of HDV infection among people with HIV/HBV in the US. We performed a cross-sectional study among adults with HIV/HBV coinfection receiving care at eight sites within the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) between 1996 and 2019. Among patients with available serum/plasma specimens, we selected the first specimen on or after their initial HBV qualifying test. All samples were tested for HDV IgG antibody and HDV RNA. Multivariable log-binomial generalized linear models were used to estimate prevalence ratios (PRs) with 95% CIs of HDV IgG antibody-positivity associated with determinants of interest (age, injection drug use [IDU], high-risk sexual behaviour). Among 597 adults with HIV/HBV coinfection in CNICS and available serum/plasma samples (median age, 43 years; 89.9% male; 52.8% Black; 42.4% White), 24/597 (4.0%; 95% CI, 2.4%-5.6%) were HDV IgG antibody-positive, and 10/596 (1.7%; 95% CI, 0.6%-2.7%) had detectable HDV RNA. In multivariable analysis, IDU was associated with exposure to HDV infection (adjusted PR = 2.50; 95% CI, 1.09-5.74). In conclusion, among a sample of adults with HIV/HBV coinfection in care in the US, 4.0% were HDV IgG antibody-positive, among whom 41.7% had detectable HDV RNA. History of IDU was associated with exposure to HDV infection. These findings emphasize the importance of HDV testing among persons with HIV/HBV coinfection, especially those with a history of IDU.

Clinical and Behavioral Outcomes for Transgender Women Engaged in HIV Care: Comparisons to Cisgender Men and Women in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) Cohort.

Describe health of transgender women (TW) with HIV vs. cisgender men and women (CM, CW) in a U.S. HIV care cohort. Data were from Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), 2005-2022. TW were identified using clinical data/identity measures. PWH (n = 1285) were included in analyses (275 TW, 547 CM, 463 CW). Cross-sectional multivariable analyses compared HIV outcomes/co-morbidities between TW/CM and TW/CW, and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were estimated. TW had poorer adherence (> 90% adherent; aOR 0.57; 95%CI 0.38, 0.87) and were more likely to miss ≥ 3 visits in the past year than CM (aOR 1.50, 95%CI 1.06, 2.10); indicated more anxiety compared to both CM and CW (p ≤ 0.001, p = 0.02); hepatitis C infection (p = 0.03) and past-year/lifetime substance treatment (p = 0.004/p = 0.001) compared to CM; and substance use relative to CW. TW with HIV differed in HIV clinical outcomes and co-morbidities from CM and CW.

Immunisation rates and predictors of undervaccination in infants with CHD.

Vaccination coverage for infants with CHD is unknown, yet these patients are at high risk for morbidity and mortality associated with vaccine-preventable illnesses. We determined vaccination rates for this population and identified predictors of undervaccination. We prospectively enrolled infants with CHD born between 1 January, 2012 and 31 December, 2015, seen in a single-centre cardiology clinic between 15 February, 2016 and 28 February, 2017. We assessed vaccination during the first year of life. Subjects who by age 1 year received all routine immunisations recommended during the first 6 months of life were considered fully vaccinated. We also evaluated influenza vaccination during subjects' first eligible influenza season. We obtained immunisation histories from primary care providers and collected demographic and clinical data via a parent survey and chart review. We used multivariable logistic regression to identify predictors of undervaccination. Among 260 subjects, only 60% were fully vaccinated. Vaccination rates were lowest for influenza (64.6%), rotavirus (71.1%), and Haemophilus influenzae type b (79.3%). Cardiac surgery with cardiopulmonary bypass during the first year of life was associated with undervaccination (51.5% versus 76.4% fully vaccinated, adjusted odds ratio 2.1 [95% confidence interval 1.1-3.9]). Other predictors of undervaccination were out-of-state primary care (adjusted odds ratio 2.7 [1.5-4.9]), multiple comorbidities (≥2 versus 0-1, adjusted odds ratio 2.0 [1.1-3.6]), and hospitalisation for >25% of the first year of life (>25% versus ≤25%, adjusted odds ratio 2.1 [1.1-3.9]). Targeted quality improvement initiatives focused on improving vaccination coverage for these infants, especially surrounding cardiac surgery, are needed.

Approach to the Febrile Infant (<3 Months).

ABSTRACT: Evaluation and management of the febrile infant has long been an area of variability. Recent guidelines were released by the American Academy of Pediatrics in August 2021 to help provide evidence-based clinical guidelines to decrease variability and improve outcomes.1 These guidelines largely focus on management and treatment guidelines for 3 age groups: 8 to 21 days, 22 to 28 days, and 29 to 60 days. The inclusion criteria for these guidelines are previously healthy, term infants born at 37 weeks gestation or later, with a temperature of 100.4°F (38°C) or higher. The most significant changes to historical practice are in the 22- to 28-day and 29- to 60-day age groups. If initial laboratory work is reassuring, patients may not need cerebrospinal fluid studies, and patients may be monitored at home or at the hospital using shared decision-making with the family.

Syphilis Testing and Diagnosis Among People With Human Immunodeficiency Virus (HIV) Engaged in Care at 4 US Clinical Sites, 2014-2018.

BACKGROUND: Despite rising rates of syphilis among people with human immunodeficiency virus (HIV; PWH) in the United States, there is no optimal syphilis screening frequency or prioritization. METHODS: We reviewed records of all PWH in care between 1 January 2014 and 16 November 2018 from 4 sites in the Centers for AIDS Research Network of Integrated Clinical Systems Cohort (CNICS; N = 8455). We calculated rates of syphilis testing and incident syphilis and used Cox proportional hazards models modified for recurrent events to examine demographic and clinical predictors of testing and diagnosis. RESULTS: Participants contributed 29 568 person-years of follow-up. The rate of syphilis testing was 118 tests per 100 person-years (95% confidence interval [CI]: 117-119). The rate of incident syphilis was 4.7 cases per 100 person-years (95% CI: 4.5-5.0). Syphilis diagnosis rates were highest among younger cisgender men who have sex with men and transgender women, Hispanic individuals, people who inject drugs, and those with detectable HIV RNA, rectal infections, and hepatitis C. CONCLUSIONS: We identified PWH who may benefit from more frequent syphilis testing and interventions for syphilis prevention.

Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19.

BACKGROUND: There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. OBJECTIVE: Develop evidence-based, rapid, living guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. METHODS: In March 2020, the Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise to regularly review the evidence and make recommendations about the treatment and management of persons with COVID-19. The process used a living guideline approach and followed a rapid recommendation development checklist. The panel prioritized questions and outcomes. A systematic review of the peer-reviewed and grey literature was conducted at regular intervals. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. RESULTS: Based on the most recent search conducted on May 31, 2022, the IDSA guideline panel has made 30 recommendations for the treatment and management of the following groups/populations: pre- and post-exposure prophylaxis, ambulatory with mild-to-moderate disease, hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines. CONCLUSIONS: At the inception of its work, the panel has expressed the overarching goal that patients be recruited into ongoing trials. Since then, many trials were done which provided much needed evidence for COVID-19 therapies. There still remain many unanswered questions as the pandemic evolved which we hope future trials can answer.

Current Antiretroviral Treatment Among People With Human Immunodeficiency Virus in the United States: Findings from the Centers for AIDS Research Network of Integrated Clinic Systems Cohort.

Among 14 049 people with human immunodeficiency virus in care in 2019-2020, 96% were treated with antiretroviral therapy (ART). Current antiretroviral treatment patterns highlight high uptake of guideline-recommended ART regimens including second-generation integrase strand transfer inhibitors (dolutegravir and bictegravir) and tenofovir alafenamide, especially in antiretroviral-naive individuals initiating ART.

Utility of Broad-Range PCR Sequencing for Infectious Diseases Clinical Decision Making: a Pediatric Center Experience.

Broad-range PCR (BRPCR) sequencing is a promising tool for diagnosis of infectious conditions when traditional microbiologic strategies fail to identify a pathogen. Data on the optimal clinical scenarios in which to use this tool are limited. We assessed, via retrospective chart review, the rate of organism identification and impact on clinical management from BRPCR testing sent from our quaternary care children's hospital between February 2010 and June 2020. A total of 382 samples were sent from 269 individual patients. A total of 200 (74.3%) patients were immunocompromised. Median age at time of sample collection was 10.0 years (interquartile range, 4.2 to 15.8). A total of 254/377 (64.7%) samples were from patients known to be on ≥1 antimicrobial in the 24 h prior to sample collection. A total of 112/382 (29.3%) samples were from patients ultimately diagnosed with a bacterial or fungal infection by another testing modality. The most common sample types were bronchoalveolar lavage (BAL) fluid (45), lung tissue (41), and bone (39). An organism was identified from 83 (21.7%) samples, but results from only 19 (5.0%) samples led to a change in management. Organisms were identified from 18 (40%) BAL samples; only 2 (4.4%) were judged to be clinically significant. A total of 4/12 (33.3%) samples from cardiac hardware changed clinical management. We found that only 5% of BRPCR results influenced antimicrobial management in a diverse pediatric cohort. Our findings suggest that the impact on clinical management varied widely by sample type. Additional work is necessary to characterize the ideal clinical scenarios in which BRPCR should be used.

Hepatitis C coinfection and extrahepatic cancer incidence among people living with HIV.

OBJECTIVES: We assessed the incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct-acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection. DESIGN: Our study cohort included adults who initiated HIV care at a CNICS site in the US during 1995-2017, excluding those with previous cancer and without HCV testing. METHODS: We used Cox regression to estimate hazard ratios for extrahepatic cancer incidence among patients with HIV/HCV coinfection compared with those with HIV monoinfection. Standardized morbidity ratio (SMR) weights were used to create a 'pseudopopulation' in which all patients were treated with antiretroviral therapy (ART), and to compare extrahepatic cancer incidence among patients with untreated HIV/HCV coinfection with the incidence that would have been observed if they had been successfully treated for HCV. RESULTS: Of 18 422 adults, 1775 (10%) had HCV RNA and 10 899 (59%) were on ART at baseline. Incidence rates of any extrahepatic cancer among patients with HIV/HCV coinfection and HIV monoinfection were 1027 and 771 per 100 000 person-years, respectively. In SMR-weighted analyses, the risk of any extrahepatic cancer among patients with untreated HCV coinfection at baseline was similar to the risk if they had been successfully treated for HCV. Patients with untreated HCV coinfection at baseline had higher incidence of kidney, lung and inflammation-related cancers than if their HCV had been successfully treated, but these associations were not statistically significant. CONCLUSIONS: We did not find evidence that treating HCV coinfection with DAAs would reduce the incidence of extrahepatic cancers among people with HIV receiving ART.

Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort.

BACKGROUND: People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH. METHODS: We assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time-updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack-years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency. RESULTS: During a median of 3.6 years of follow-up, 213 PWH developed a VTE. One-third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02-2.03) and former (HR: 1.44, 95% CI: 0.99-2.07) smokers compared to PWH who never smoked. Additionally, total pack-years among ever-smokers (HR: 1.10 per 5 pack-years; 95% CI: 1.03-1.18) was associated with incident VTE in a dose-dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11-1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE. CONCLUSIONS: Current smoking and pack-year smoking history were dose-dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.

Comorbidities Associated with Hospitalization and Progression Among Adolescents with Symptomatic Coronavirus Disease 2019.

OBJECTIVE: To identify subgroups likely to benefit from monoclonal antibody and antiviral therapy by evaluating the relationship between comorbidities and hospitalization among US adolescents with symptomatic coronavirus disease 2019 (COVID-19). STUDY DESIGN: We analyzed the relationship between presence of comorbidities and need for hospitalization within 28 days of COVID-19 diagnosis for adolescents aged 12-17 years listed in the Pediatric COVID-19 US registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes, immunosuppressive disease or treatment, sickle cell disease (SCD), heart disease, neurologic disease/neurodevelopmental disorders, and pulmonary disease (excluding patients with mild asthma). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization. RESULTS: A total of 1877 patients met our inclusion criteria, of whom 284 (15%) were hospitalized within 28 days of their COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: SCD (aOR, 6.9; 95% CI, 3.0-15.9), immunocompromising condition (aOR, 6.4; 95% CI, 3.8-10.8), obesity (aOR, 3.2; 95% CI, 2.1-4.9), diabetes (aOR, 3.0; 95% CI, 1.4-6.2), neurologic disease (aOR, 2.8; 95% CI, 1.8-4.3), and pulmonary disease (excluding mild asthma) (aOR, 1.9; 95% CI, 1.2-3.1). Heart disease and CKD were not independently associated with hospitalization. CONCLUSIONS: SCD, immunocompromising conditions, obesity, diabetes, neurologic disease, and pulmonary disease (excluding mild asthma) were associated with hospitalization for symptomatic COVID-19. Adolescents with acute COVID-19 and these comorbidities should be prioritized for consideration of therapy to avert hospitalization.

Risk of HCC With Hepatitis B Viremia Among HIV/HBV-Coinfected Persons in North America.

BACKGROUND AND AIMS: Chronic HBV is the predominant cause of HCC worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multicohort study of individuals coinfected with HIV/HBV. APPROACH AND RESULTS: We included persons coinfected with HIV/HBV within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995-2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted HRs (aHRs [95% CIs]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, HCV), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA). Among 8,354 individuals coinfected with HIV/HBV (median age, 43 years; 93% male; 52.4% non-White), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5-2.1] events/1,000 person-years). Risk factors for HCC included age 40-49 years (aHR, 1.97 [1.22-3.17]), age ≥50 years (aHR, 2.55 [1.49-4.35]), HCV coinfection (aHR, 1.61 [1.07-2.40]), and heavy alcohol use (aHR, 1.52 [1.04-2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56-1.43]) and time-updated CD4+ percentage <14% (aHR, 1.03 [0.56-1.90]) were not. The risk of HCC was increased with time-updated HBV DNA >200 IU/mL (aHR, 2.22 [1.42-3.47]) and was higher with each 1.0 log10 IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05-1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1 year significantly reduced HCC risk (aHR, 0.42 [0.24-0.73]). CONCLUSION: Individuals coinfected with HIV/HBV on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.

Epidemiology and outcomes of invasive aspergillosis among pediatric immunocompromised patients: A 12-year single-center experience.

Invasive aspergillosis (IA) remains a common cause of mortality in pediatric immunocompromised populations. Much of our knowledge of IA stems from adult literature. We conducted a retrospective evaluation of cases of proven or probable IA, defined according to the 2019 EORTC/MSG criteria, in patients with underlying immunocompromising conditions at Boston Children's Hospital from January 1, 2007 to January 1, 2019. We estimated survival curves over 12 weeks using the Kaplan-Meier method for all-cause mortality, and we used univariate Cox proportional hazards modeling to evaluate for mortality risk factors. We identified 59 cases, 29% with proven and 71% with probable IA. Pulmonary IA was the most common presentation (78%). The median age at diagnosis was 11 years (range, 0.5-28). Hematopoietic cell transplantation (HCT) was the most frequent predisposing underlying condition (41%). Among affected patients, 44.8% were neutropenic and 59.3% were lymphopenic at diagnosis. The 12-week all-cause mortality rate was 25.4%; HCT recipients comprised the majority of deaths (9/15) with a hazard ratio of 2.47 [95% CI, 0.87-6.95]. No patients with congenital immunodeficiencies (n = 8) died within 12 weeks of IA diagnosis. Other risk factors that were significantly associated with mortality included mechanical ventilation at diagnosis, intensive care unit stay, and lymphopenia; treatment with an Aspergillus-active azole was associated with decreased mortality.In conclusion, our study found that in pediatric immunocompromised hosts, IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the HCT population. LAY ABSTRACT: This study explores the epidemiology, outcomes and predictors of mortality of invasive aspergillosis (IA) at a high-volume pediatric center for immunocompromised hosts. Much of our understanding of pediatric IA is extrapolated from the adult literature. Our study found that IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the hematopoietic cell transplantation study cohort.

Multicenter Development and Validation of a Model for Predicting Retention in Care Among People with HIV.

Predictive analytics can be used to identify people with HIV currently retained in care who are at risk for future disengagement from care, allowing for prioritization of retention interventions. We utilized machine learning methods to develop predictive models of retention in care, defined as no more than a 12 month gap between HIV care appointments in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. Data were split longitudinally into derivation and validation cohorts. We created logistic regression (LR), random forest (RF), and gradient boosted machine (XGB) models within a discrete-time survival analysis framework and compared their performance to a baseline model that included only demographics, viral suppression, and retention history. 21,267 Patients with 507,687 visits from 2007 to 2018 were included. The LR model outperformed the baseline model (AUC 0.68 [0.67-0.70] vs. 0.60 [0.59-0.62], P < 0.001). RF and XGB models had similar performance to the LR model. Top features in the LR model included retention history, age, and viral suppression.