Incidence, Clearance, and Persistence of Penile High-Risk Human Papillomavirus Among Rwandan Men Who Have Sex With Men.

BACKGROUND: Little is known about penile high-risk human papillomavirus (hrHPV) among men who have sex with men (MSM) in low- and middle-income countries. We aimed to determine the incidence, clearance, and persistence of penile hrHPV among Rwandan MSM. METHODS: We enrolled 350 MSM (345 with valid human papillomavirus [HPV] results) aged ≥18 years. At each visit (6-12 months apart), we collected penile PreservCyt specimens and blood for HPV and HIV testing, as well as sociodemographic and behavioral variables. HPV testing was performed with the Ampfire assay. Penile hrHPV incidence and clearance per 1000 person-months of follow-up, as well as prevalent and incident persistence, were computed and compared by HIV status. RESULTS: The mean (SD) age was 27.7 (6.7) years and 19.4% were living with HIV. Penile hrHPV incidence was 34.8 (95% CI, 29.1-41.8) per 1000 person-months of follow-up. HPV-16 (11.7; 95% CI, 9.26-14.9) and HPV-59 (6.1; 95% CI, 4.52-8.39) had the highest incidence rates. Prevalent and incident persistence was 47.5% and 46.6%, respectively. HPV-66 (33.3%), HPV-52 (30.8%), and HPV-16 (29.2%) had the highest prevalent persistence and HPV-33 (53.8%), HPV-31 (46.7%), and HPV-16 (42.6%) the highest incident persistence. No differences were found by HIV status except for HPV-45 (higher in MSM with HIV). CONCLUSIONS: We found high incidence and prevalent/incident persistence of penile hrHPV among Rwandan MSM. This highlights the importance of preventive strategies for HPV-associated anogenital cancers.

Development and validation of MRI PDFF Cut-offs for living liver donor eligibility assessment.

Hepatic steatosis (HS) criteria for living donor liver transplantation (LDLT) donor eligibility should be based on large droplet fat as per Banff consensus recommendations. We aimed to establish MRI PDFF cut-offs for HS assessment in potential LDLT donors. This retrospective study included consecutive potential LDLT donors who underwent MRI and liver biopsy between 2013 and 2023 at two tertiary institutions, each as development (n=3062; 2015 men; median [interquartile range] age of 32 [25-38] years) and external validation (n=472; 287 men; 35 [26-44] years) datasets. PDFF was measured using dedicated MRI sequences. Histologic HS defined as large droplet fat fraction was used as the reference standard. Dual PDFF cut-offs aimed at 95% sensitivity or 95% specificity, for diagnosing histologic HS of ≥10%, ≥20%, ≥30%, and ≥40%, were determined in the development dataset using ten-fold cross validation. The cut-offs were then validated in the external validation dataset. Equation for estimating histologic HS from PDFF was also derived using linear regression. The PDFF cut-offs for histologic HS of ≥10%, ≥20%, ≥30%, and ≥40%, targeting 95% sensitivity, were 3.7%, 5.5%, 8.0%, and 10.0%, respectively. External validation demonstrated high sensitivities ≥ 97.9% with specificities ranging from 60.9% to 95.1%. The PDFF cut-offs targeting 95% specificity were 6.3%, 8.0%, 9.1%, and 10.1%, respectively. External validation rendered high specificities ranging from 88.5% to 95.3% with sensitivities ranging from 76.6% to 100%. For diagnosing histologic HS ≥30%, which is the most prevalently used threshold for LDLT donor eligibility assessment, the PDFF cut-offs achieved sensitivities and specificities of both over 90%. The equation of (Histologic HS=-2.95 + 1.93 * PDFF) was derived.

Performance analysis of mathematical methods used to forecast the 2022 New York City Mpox outbreak.

In mid-2022, New York City (NYC) became the epicenter of the US mpox outbreak. We provided real-time mpox case forecasts to the NYC Department of Health and Mental Hygiene to aid in outbreak response. Forecasting methodologies evolved as the epidemic progressed. Initially, lacking knowledge of at-risk population size, we used exponential growth models to forecast cases. Once exponential growth slowed, we used a Susceptible-Exposed-Infectious-Recovered (SEIR) model. Retrospectively, we explored if forecasts could have been improved using an SEIR model in place of our early exponential growth model, with or without knowing the case detection rate. Early forecasts from exponential growth models performed poorly, as 2-week mean absolute error (MAE) grew from 53 cases/week (July 1-14) to 457 cases/week (July 15-28). However, when exponential growth slowed, providing insight into susceptible population size, an SEIR model was able to accurately predict the remainder of the outbreak (7-week MAE: 13.4 cases/week). Retrospectively, we found there was not enough known about the epidemiological characteristics of the outbreak to parameterize an SEIR model early on. However, if the at-risk population and case detection rate were known, an SEIR model could have improved accuracy over exponential growth models early in the outbreak.

Improving radiomics reproducibility using deep learning-based image conversion of CT reconstruction algorithms in hepatocellular carcinoma patients.

OBJECTIVES: CT reconstruction algorithms affect radiomics reproducibility. In this study, we evaluate the effect of deep learning-based image conversion on CT reconstruction algorithms. METHODS: This study included 78 hepatocellular carcinoma (HCC) patients who underwent four-phase liver CTs comprising non-contrast, late arterial (LAP), portal venous (PVP), and delayed phase (DP), reconstructed using both filtered back projection (FBP) and advanced modeled iterative reconstruction (ADMIRE). PVP images were used to train a convolutional neural network (CNN) model to convert images from FBP to ADMIRE and vice versa. LAP, PVP, and DP images were used for validation and testing. Radiomic features were extracted for each patient with a semi-automatic segmentation tool. We used concordance correlation coefficients (CCCs) to evaluate the radiomics reproducibility for original FBP (oFBP) vs. original ADMIRE (oADMIRE), oFBP vs. converted FBP (cFBP), and oADMIRE vs. converted ADMIRE (cADMIRE). RESULTS: In the test group including 30 patients, the CCC and proportion of reproducible features (CCC ≥ 0.85) for oFBP vs. oADMIRE were 0.65 and 32.9% (524/1595) for LAP, 0.65 and 35.9% (573/1595) for PVP, and 0.69 and 43.8% (699/1595) for DP. For oFBP vs. cFBP, the values increased to 0.92 and 83.9% (1339/1595) for LAP, 0.89 and 71.0% (1133/1595) for PVP, and 0.90 and 79.7% (1271/1595) for DP. Similarly, for oADMIRE vs. cADMIRE, the values increased to 0.87 and 68.1% (1086/1595) for LAP, 0.91 and 82.1% (1309/1595) for PVP, and 0.89 and 76.2% (1216/1595) for DP. CONCLUSIONS: CNN-based image conversion between CT reconstruction algorithms improved the radiomics reproducibility of HCCs. CLINICAL RELEVANCE STATEMENT: This study demonstrates that using a CNN-based image conversion technique significantly improves the reproducibility of radiomic features in HCCs, highlighting its potential for enhancing radiomics research in HCC patients. KEY POINTS: Radiomics reproducibility of HCC was improved via CNN-based image conversion between two different CT reconstruction algorithms. This is the first clinical study to demonstrate improvements across a range of radiomic features in HCC patients. This study promotes the reproducibility and generalizability of different CT reconstruction algorithms in radiomics research.

Risk of hematologic malignant neoplasms from head CT radiation in children and adolescents presenting with minor head trauma: a nationwide population-based cohort study.

OBJECTIVES: The carcinogenic risks of CT radiation in children and adolescents remain debated. We aimed to assess the carcinogenic risk of CTs performed in children and adolescents with minor head trauma. METHODS: In this nationwide population-based cohort study, we included 2,411,715 patients of age 0-19 with minor head trauma from 2009 to 2017. We excluded patients with elevated cancer risks or substantial past medical radiation exposure. Patients were categorized into CT-exposed or CT-unexposed group according to claim codes for head CT. The primary outcome was development of hematologic malignant neoplasms. Secondary outcomes included development of malignant solid neoplasms and benign neoplasms in the brain. We measured the incidence rate ratio (IRR) and incidence rate difference (IRD) using G-computation with Poisson regression adjusting for age, sex, hospital setting, and the type of head trauma. RESULTS: Hematologic malignant neoplasms developed in 100 of 216,826 patients during 1,303,680 person-years in the CT-exposed group and in 808 of 2,194,889 patients during 13,501,227 person-years in the CT-unexposed group. For hematologic malignant neoplasms, the IRR was 1.29 (95% CI, 1.03-1.60) and the IRD was 1.71 (95% CI, 0.04-3.37) per 100,000 person-years at risk. The majority of excess hematologic malignant neoplasms were leukemia (IRR, 1.40 [98.3% CI, 1.05-1.87]; IRD, 1.59 [98.3% CI, 0.02-3.16] per 100,000 person-years at risk). There were no between-group differences for secondary outcomes. CONCLUSIONS: Radiation exposure from head CTs in children and adolescents with minor head trauma was associated with an increased incidence of hematologic malignant neoplasms. CLINICAL RELEVANCE STATEMENT: Our study provides a quantitative grasp of the risk conferred by CT examinations in children and adolescents, thereby providing the basis for cost-benefit analyses and evidence-driven guidelines for patient triaging in head trauma. KEY POINTS: • This nationwide population-based cohort study showed that radiation exposure from head CTs in children and adolescents was associated with a higher incidence of hematologic malignant neoplasms. • The incidence rate of hematologic malignant neoplasms in the CT-exposed group was 29% higher than that in the CT-unexposed group (IRR, 1.29 [95% CI, 1.03-1.60]), and there were approximately 1.7 excess neoplasms per 100,000 person-years at risk in the CT-exposed group (IRD, 1.71 [0.04-3.37]). • Our study provides a quantified grasp of the risk conferred by CT examinations in children and adolescents, while controlling for biases observed in previous studies via specifying CT indication and excluding patients with predisposing conditions for cancer development.

Effect of a Male-Targeted Digital Decision Support Application Aimed at Increasing Linkage to HIV Care Among Men: Findings from the HITS Cluster Randomized Clinical Trial in Rural South Africa.

Linkage to HIV care remains suboptimal among men. We investigated the effectiveness of a male-targeted HIV-specific decision support app, Empowering People through Informed Choices for HIV (EPIC-HIV), on increasing linkage to HIV care among men in rural South Africa. Home-Based Intervention to Test and Start (HITS) was a multi-component cluster-randomized controlled trial conducted among 45 communities in uMkhanyakude, KwaZulu-Natal. The development of EPIC-HIV was guided by self-determination theory and human-computer interaction design to increase intrinsic motivation to seek HIV testing and care among men. EPIC-HIV was offered in two stages: EPIC-HIV 1 at the time of home-based HIV counseling and testing (HBHCT), and EPIC-HIV 2 at 1 month after a positive HIV diagnosis if not linked to care. Sixteen communities were randomly assigned to the arms to receive EPIC-HIV, and 29 communities to the arms without EPIC-HIV. Among all eligible men, we compared linkage to care (initiation or resumption of antiretroviral therapy after > 3 months of care interruption) at local clinics within 1 year of a home visit, ascertained from individual clinical records. Intention-to-treat analysis was performed using modified Poisson regression with adjustment for receiving another intervention (i.e., financial incentives) and clustering at the community level. We also conducted a satisfaction survey for EPIC-HIV 2. A total of 13,894 men were eligible (i.e., aged ≥ 15 years and resident in the 45 communities). The mean age was 34.6 (±16.8) years, and 65% were married or in an informal union. Overall, 20.7% received HBHCT, resulting in 122 HIV-positive and 6 discordant tests. Among these, 54 men linked to care within 1 year after HBHCT. Additionally, of the 13,765 eligible participants who did not receive HBHCT or received HIV-negative results, 301 men linked to care within 1 year. Overall, only 13 men received EPIC-HIV 2. The proportion of linkage to care did not differ between the arms randomized to EPIC-HIV and those without EPIC-HIV (adjusted risk ratio = 1.05; 95% CI:0.86-1.29). All 13 men who used EPIC-HIV 2 reported the app was acceptable, user-friendly, and useful for getting information on HIV testing and treatment. The reach was low, although the acceptability and usability of the app were very high among those who engaged with it. Enhanced digital support applications could form part of interventions to increase knowledge of HIV treatment among men. Clinical Trial Number: ClinicalTrials.gov # NCT03757104.

Coprevalence and associations of diabetes mellitus and hypertension among people living with HIV/AIDS in Cameroon.

BACKGROUND: The association between HIV infection and increased cardiometabolic risk, attributed to chronic inflammation in people living with HIV (PLWH) and/or antiretroviral therapy (ART) effects, has been inconsistent. In this study, we aimed to assess the associations of HIV-related factors with hypertension (HTN) and type-2 diabetes mellitus (T2DM), and the potential mediation effects of body mass index (BMI) in the associations between ART use and HTN or T2DM in PLWH in Cameroon. METHODS: A cross-sectional study was conducted with 14,119 adult PLWH from Cameroon enrolled in the International epidemiology Databases to Evaluate AIDS (IeDEA) between 2016 and 2021. HTN was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg and/or current use of antihypertensive medication, while T2DM was defined as fasting blood sugar ≥ 126 mg/dL and/or use of antidiabetic medications. Univariable and multivariable multinomial logistic regression analyses examined the associations of factors with HTN alone, T2DM alone, and both (HTN + T2DM). Mediation analyses were conducted to assess the potential mediation roles of BMI, while controlling for age, sex, and smoking. RESULTS: Of the 14,119 participants, 9177 (65%) were women, with a median age of 42 (25th-75th percentiles: 35-51) years. Age > 50 years was associated with HTN alone, T2DM alone, and HTN + T2DM compared to the age group 19-29 years. Men had higher odds of having HTN + T2DM. Overweight and obesity were predictors of HTN alone compared to being underweight. WHO stages II and III HIV disease were inversely associated with HTN alone compared to stage I. The odds of diabetes alone were lower with ART use. BMI partially mediated the association between ART use and hypertension, with a proportion of mediation effect of 49.6% (all p < 0.02). However, BMI did not mediate the relationship between ART use and diabetes. CONCLUSIONS: Traditional cardiovascular risk factors were strongly associated with hypertension among PLWH, while HIV-related exposures had smaller associations. BMI partially mediated the association between ART use and hypertension. This study emphasizes the importance of screening, monitoring, and managing HTN and T2DM in older, male, and overweight/obese PLWH. Further research on the associations of HIV disease stage and ART use with HTN and T2DM is warranted.

TAS2R38 bitterness receptor genetic variation is associated with diet quality in Koreans.

Genetic variation in the bitter taste receptor gene taste receptor type 2, member 38 (TAS2R38) is associated with an individual's bitter taste sensitivity, food preference and consumption, which may also influence overall diet quality. This study aims to determine whether the TAS2R38 bitter taste receptor genetic variation is associated with overall diet quality using the Korean Healthy Eating Index (KHEI). A total of 41,839 individuals from the Korean Genome and Epidemiology Study were analyzed for their TAS2R38 diplotypes (rs713598, rs1726866, and rs10246939), general characteristics, and KHEI scores by obesity status. Results revealed that in the non-obese group, individuals with the AVI/AVI diplotype had a significantly higher score of 'ratio of white meat to red meat' than individuals with the PAV/* diplotype (3.89 ± 3.23 vs. 3.79 ± 3.18, adjusted p = 0.029). However, obese individuals with the PAV/* diplotype showed a significantly higher level of the mean score of 'moderation' (19.32 ± 5.82 vs. 18.92 ± 5.80, adjusted p = 0.026) and total KHEI score (61.07 ± 12.19 vs. 60.52 ± 12.29, adjusted p = 0.008) than those with the AVI/AVI diplotype. Finally, an interactive effect between bitterness genetic variation and obesity level was observed in those scores of 'ratio of white meat to red meat' (adjusted p = 0.007), 'moderation' (adjusted p = 0.013), and total KEHI (adjusted p = 0.007). In conclusion, TAS2R38 genetic variation is associated with overall diet quality in Koreans, which is more evident in the obese group.

Impact of schizophrenia GWAS loci converge onto distinct pathways in cortical interneurons vs glutamatergic neurons during development.

Remarkable advances have been made in schizophrenia (SCZ) GWAS, but gleaning biological insight from these loci is challenging. Genetic influences on gene expression (e.g., eQTLs) are cell type-specific, but most studies that attempt to clarify GWAS loci's influence on gene expression have employed tissues with mixed cell compositions that can obscure cell-specific effects. Furthermore, enriched SCZ heritability in the fetal brain underscores the need to study the impact of SCZ risk loci in specific developing neurons. MGE-derived cortical interneurons (cINs) are consistently affected in SCZ brains and show enriched SCZ heritability in human fetal brains. We identified SCZ GWAS risk genes that are dysregulated in iPSC-derived homogeneous populations of developing SCZ cINs. These SCZ GWAS loci differential expression (DE) genes converge on the PKC pathway. Their disruption results in PKC hyperactivity in developing cINs, leading to arborization deficits. We show that the fine-mapped GWAS locus in the ATP2A2 gene of the PKC pathway harbors enhancer marks by ATACseq and ChIPseq, and regulates ATP2A2 expression. We also generated developing glutamatergic neurons (GNs), another population with enriched SCZ heritability, and confirmed their functionality after transplantation into the mouse brain. Then, we identified SCZ GWAS risk genes that are dysregulated in developing SCZ GNs. GN-specific SCZ GWAS loci DE genes converge on the ion transporter pathway, distinct from those for cINs. Disruption of the pathway gene CACNA1D resulted in deficits of Ca2+ currents in developing GNs, suggesting compromised neuronal function by GWAS loci pathway deficits during development. This study allows us to identify cell type-specific and developmental stage-specific mechanisms of SCZ risk gene function, and may aid in identifying mechanism-based novel therapeutic targets.

Staging Chest CT in Patients With Early-Stage Colon Cancer: Analysis of Impact on Survival Using Inverse Probability Weighting and Causal Diagram.

BACKGROUND. Staging chest CT has been shown to have negligible diagnostic yield for detecting lung metastases in patients with early-stage colon cancer. Nonetheless, staging chest CT may have potential survival benefits, including opportunistic screening of comorbidity and provision of a baseline examination for future comparisons. Evidence is lacking regarding the impact of staging chest CT on survival in patients with early-stage colon cancer. OBJECTIVE. The purpose of this study was to determine whether the performance of staging chest CT affects survival in patients with early-stage colon cancer. METHODS. This retrospective study included patients with early-stage colon cancer (defined as clinical stage 0 or I on staging abdominal CT) at a single tertiary hospital between January 2009 and December 2015. Patients were divided into two groups according to the presence of a staging chest CT examination. To ensure comparability between the two groups, inverse probability weighting was applied to adjust for the confounders derived from a causal diagram. The between-group differences in adjusted restricted mean survival time at 5 years were measured for overall survival, relapse-free survival, and thoracic metastasis-free survival. Sensitivity analyses were performed. RESULTS. A total of 991 patients (618 men and 373 women; median age, 64 years [IQR, 55-71 years]) were included: 606 patients (61.2%) had staging chest CT. For overall survival, the difference between groups in restricted mean survival time at 5 years was not significant (0.4 months [95% CI, -0.8 to 2.1 months]). The differences between groups in restricted mean survival at 5 years were also not significant for relapse-free survival (0.4 months [95% CI, -1.1 to 2.3 months]) and for thoracic metastasis-free survival (0.6 months [95% CI, -0.8 to 2.4 months]). Similar results were observed in sensitivity analyses that tested 3- and 10-year RMST differences, excluded patients who underwent FDG PET/CT during staging workup, and added treatment decision (surgery vs no surgery) to the causal diagram. CONCLUSION. The use of staging chest CT did not affect survival in patients with early-stage colon cancer. CLINICAL IMPACT. Staging chest CT may be omitted from the staging workup for patients with colon cancer of clinical stage 0 or I.

How severe would prioritization-induced bottlenecks need to be offset the benefits from prioritizing COVID-19 vaccination to those most at risk in New York City?

BACKGROUND: Prioritization of higher-risk people for COVID-19 vaccination could prevent more deaths, but could slow vaccination speed. We used mathematical modeling to examine the trade-off between vaccination speed and prioritization for individuals age 65+ and essential workers. METHODS: We used a stochastic, discrete-time susceptible-exposed-infected-recovered (SEIR) model with age- and comorbidity-adjusted COVID-19 outcomes (infections, hospitalizations, and deaths). The model was calibrated to COVID-19 hospitalizations, ICU census, and deaths in NYC. We assumed 10,000 vaccinations per day, initially restricted to healthcare workers and nursing home populations, and subsequently expanded to other populations at alternative times (4, 5, or 6 weeks after vaccine launch) and speeds (20,000, 50,000, 100,000, or 150,000 vaccinations per day), as well as prioritization options (+/- prioritization of people age 65+ and essential workers). In sensitivity analyses, we examined the effect of a SARS-COV-2 variant with greater transmissibility. RESULTS: To be beneficial, prioritization must not create a bottleneck that decreases vaccination speed by > 50% without a more transmissible variant, or by > 33% with the emergence of the more transmissible variant. More specifically, prioritizing people age 65+ and essential workers increased the number of lives saved per vaccine dose delivered: 3000 deaths could be averted by delivering 83,000 vaccinations per day without prioritization or 50,000 vaccinations per day with prioritization. Other tradeoffs involve vaccination speed and timing. Compared to the slowest-examined vaccination speed of 20,000 vaccinations per day, achieving the fastest-examined vaccination speed of 150,000 vaccinations per day would avert additional 313,700 (28.6%) infections and 1693 (24.1%) deaths. Emergence of a more transmissible variant would double COVID-19 infections, hospitalizations, and deaths over the first 6 months of vaccination. The fastest-examined vaccination speed could only offset the harm of the more transmissible variant if achieved within 5 weeks of vaccine launch. CONCLUSIONS: Faster vaccination speed with sooner vaccination expansion would save more lives. Prioritization of COVID-19 vaccines to higher-risk populations would be more beneficial only if it does not create an excessive vaccine delivery bottleneck.

Ethical considerations in using a smartphone-based GPS app to understand linkages between mobility patterns and health outcomes: The example of HIV risk among mobile youth in rural South Africa.

Smartphones with Global Positioning System (GPS) apps offer simple and accurate tools to collect data on human mobility. However, their associated ethical challenges remain to be assessed. We used the Emanuel framework to assess the ethical concerns of using smartphone GPS to record mobility patterns of young adults in rural South Africa for a larger study on mobility and HIV risk (Sesikhona). We conducted four focus groups (FGDs) with individuals eligible for the Sesikhona study. FGD data were coded using the Emanuel framework. Participants perceived use of smartphone GPS to study human mobility and HIV risk as valuable. They raised concerns about invasion of privacy and confidentiality. Also mentioned were risk/benefit ratio, informed consent and ongoing respect. Concerns expressed provided a useful evidence-base for the development of a guide to inform future participants about ethical issues arising in the use of GPS technology to track mobility and health-related issues.

Do the oral health-related quality of life and the magnitude of its association with malocclusion differ by developmental stages of schoolchildren?

INTRODUCTION: As schoolchildren go through multiple developmental periods, their oral health-related quality of life (OHRQOL) level may change over time. It is important to understand the association between malocclusion and OHRQOL in treatment planning for schoolchildren. This study aimed to examine OHRQOL and its association with malocclusion among schoolchildren at different developmental stages. METHODS: Data from a representative sample of 2010 Korean schoolchildren aged 7-17 years were analyzed. The participants completed a self-administered questionnaire, and their orthodontic treatment needs were assessed by a dentist. OHRQOL was measured using the Child Oral Health Impact Profile (COHIP). Higher COHIP scores indicate better OHRQOL. RESULTS: The mean age of the sample was 11.9 ± 2.5 years, and slightly more boys (53.0%) were in the sample. The total COHIP score (P <0.001) and 4 subscale scores (P <0.01) were lower in older age groups. Compared with those who needed orthodontic treatment, children with no and borderline orthodontic treatment needs were 1.9 times (odds ratio [OR], 1.9; 95% confidence interval, 1.5-2.4) and 1.5 times (OR, 1.5; 95% confidence interval, 1.1-2.1) more likely to have a higher COHIP score, respectively. The degree of association varied across age groups: a larger effect was found in the oldest group (aged 15 years) (OR, 4.1) than in younger groups (ORs, 1.5-2.2). CONCLUSIONS: OHRQOL and the magnitude of its association with malocclusion varied by age among schoolchildren, particularly in functional and social-emotional well-being. Given the variation, schoolchildren's developmental stages should be considered in treatment planning.

CD4+ T-Cell Count at Antiretroviral Therapy Initiation in the "Treat-All" Era in Rural South Africa: An Interrupted Time Series Analysis.

BACKGROUND: South Africa implemented universal test and treat (UTT) in September 2016 in an effort to encourage earlier initiation of antiretroviral therapy (ART). METHODS: We therefore conducted an interrupted time series (ITS) analysis to assess the impact of UTT on mean CD4 count at ART initiation among adults aged ≥16 years attending 17 public sector primary care clinics in rural South Africa, between July 2014 and March 2019. RESULTS: Among 20 599 individuals (69% women), CD4 counts were available for 74%. Mean CD4 at ART initiation increased from 317.1 cells/µL (95% confidence interval [CI], 308.6 to 325.6) 1 to 8 months prior to UTT to 421.0 cells/µL (95% CI, 413.0 to 429.0) 1 to 12 months after UTT, including an immediate increase of 124.2 cells/µL (95% CI, 102.2 to 146.1). However, mean CD4 count subsequently fell to 389.5 cells/µL (95% CI, 381.8 to 397.1) 13 to 30 months after UTT but remained above pre-UTT levels. Men initiated ART at lower CD4 counts than women (-118.2 cells/µL, 95% CI, -125.5 to -111.0) throughout the study. CONCLUSIONS: Although UTT led to an immediate increase in CD4 count at ART initiation in this rural community, the long-term effects were modest. More efforts are needed to increase initiation of ART early in those living with human immunodeficiency virus, particularly men.

Adrenal Nodules Detected at Staging CT in Patients with Resectable Gastric Cancers Have a Low Incidence of Malignancy.

Background Guidelines recommending additional imaging for adrenal nodules lack relevant epidemiologic evidence. Purpose To measure the prevalence of adrenal nodules detected at staging CT in patients with potentially resectable gastric cancer and the proportion of patients with malignant nodules among them. Materials and Methods This retrospective study included 10 250 consecutive patients (median age, 63 years; interquartile range, 53-71 years; 6884 men) who underwent staging CT and had potentially resectable gastric cancer in a tertiary center (May 2003 to December 2018). All 10 250 CT studies were retrospectively reviewed, and patients with adrenal nodules (or thickening ≥10 mm) were identified to measure the prevalence of adrenal nodules. Among patients with adrenal nodules, the per-patient proportions of malignant nodules, adrenal metastasis from gastric cancer, and additional adrenal examinations were measured. A secondary analysis was performed by using data from the original CT reports. The same metrics that were used in the retrospective review were assessed. Results The prevalence of adrenal nodules was 4.5% (95% CI: 4.1, 4.9; 462 of 10 250). The proportions of malignant nodules and adrenal metastasis from gastric cancer were 0.4% ( 95% CI: 0.1, 1.6; two of 462) and 0% (95% CI: 0.0, 0.8; 0 of 462), respectively. A total of 27% of the patients (95% CI: 23, 31; 123 of 462) underwent additional adrenal examination. According to original CT reports, the prevalence of adrenal nodules and the proportions of malignant nodules, adrenal metastases from gastric cancer, and additional adrenal examination were 2.7% (95% CI: 2.4, 3.0; 272 of 10 250), 0.7% (95% CI: 0.1, 2.6; two of 272), 0% (95% CI: 0.0, 1.4; 0 of 272), and 42.6% (95% CI: 36.7, 48.8; 116 of 272), respectively. Conclusion Although adrenal nodules were detected frequently on staging CT images of patients with otherwise resectable gastric cancer, these nodules were rarely malignant. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Baumgarten in this issue.

Real-Time Infectious Disease Modeling to Inform Emergency Public Health Decision Making.

Infectious disease transmission is a nonlinear process with complex, sometimes unintuitive dynamics. Modeling can transform information about a disease process and its parameters into quantitative projections that help decision makers compare public health response options. However, modelers face methodologic challenges, data challenges, and communication challenges, which are exacerbated under the time constraints of a public health emergency. We review methods, applications, challenges and opportunities for real-time infectious disease modeling during public health emergencies, with examples drawn from the two deadliest pandemics in recent history: HIV/AIDS and coronavirus disease 2019 (COVID-19).

Incidence of malignancy in adrenal nodules detected on staging CTs of patients with potentially resectable colorectal cancer.

OBJECTIVE: To measure the prevalence of adrenal nodules detected on staging CT in patients with resectable colorectal cancer, and the proportion of patients with malignant nodules among them. METHODS: This retrospective study included 6474 patients (median age, 65; interquartile range, 56-73; 3902 men) who underwent staging CT for colorectal cancer between May 2003 and December 2018. The patients had potentially resectable colorectal cancer, including resectable hepatic or pulmonary metastases. Through retrospective CT image review, patients with adrenal nodules were identified for the prevalence of adrenal nodule. Among patients with adrenal nodules, per-patient proportions of malignant nodules, adrenal metastasis from colorectal cancer, and additional adrenal examinations (biopsy or imaging tests) were measured. A secondary analysis was performed using data from the official CT reports. RESULTS: The prevalence of adrenal nodules was 5.6% (363 of 6474; 95% CI: 5.1, 6.2). The proportions of malignant nodules and adrenal metastasis from colorectal cancer were 0.8% (3 of 363; 0.2, 2.4) and 0.3% (1 of 363; 0.0, 1.5), respectively. 6.1% (22 of 363; 3.8, 9.0) of the patients underwent additional adrenal examination. According to official CT reports, the prevalence of adrenal nodules and proportions of malignant nodules, adrenal metastasis from colorectal cancer, and additional adrenal examination were 1.9% (125 of 6474; 1.6, 2.3), 1.6% (2 of 125; 0.2, 5.7), 0% (0 of 125; 0.0, 2.9), and 10.4% (1 of 125; 5.7, 17.1), respectively. CONCLUSION: Adrenal nodules detected in staging CTs in patients with otherwise resectable colorectal cancers are rarely malignant. KEY POINTS: • Among 6474 patients who underwent staging CT and had potentially resectable colorectal cancer, 363 had adrenal nodules (≥ 10 mm) detected in retrospective CT image review. • Three out of the 363 patients with adrenal nodules detected on staging CT had malignant adrenal nodules, one of whom had metastasis from colorectal cancer.

Dose reduction potential of vendor-agnostic deep learning model in comparison with deep learning-based image reconstruction algorithm on CT: a phantom study.

OBJECTIVES: To compare the dose reduction potential (DRP) of a vendor-agnostic deep learning model (DLM, ClariCT.AI) with that of a vendor-specific deep learning-based image reconstruction algorithm (DLR, TrueFidelity™). METHODS: Computed tomography (CT) images of a multi-sized image quality phantom (Mercury v4.0) were acquired under six radiation dose levels (0.48/0.97/1.93/3.87/7.74/15.47 mGy) and were reconstructed using filtered back projection (FBP) and three strength levels of the DLR (low/medium/high). The FBP images were denoised using the DLM. For all DLM and DLR images, the detectability index (d') (a task-based detection performance metric) was obtained, under various combinations of three target sizes (10/5/1 mm), five inlets (CT value difference with the background; -895/50/90/335/1000 HU), five phantom diameters (36/31/26/21/16 cm), and six radiation dose levels. Dose reduction potential (DRP) measures the dose reduction made by using DLM or DLR, while yielding d' equivalent to that of FBP at full dose. RESULTS: The DRPs of the DLM, DLR-low, DLR-medium, and DLR-high were 86% (81-88%), 60% (46-67%), 76% (60-81%), and 87% (78-92%), respectively. For 10-mm targets, the DRP of the DLM (87%) was higher than that of all DLR algorithms (58-86%). However, for smaller targets (5 mm/1 mm), the DRPs of the DLR-high (89/88%) were greater than those of the DLM (87/84%). CONCLUSION: The dose reduction potential of the vendor-agnostic DLM was shown to be comparable to that of the vendor-specific DLR at high strength and superior to those of the DLRs at medium and low strengths. KEY POINTS: • DRP of the vendor-agnostic model was comparable to that of high-strength vendor-specific model and superior to those of medium- and low-strength models. • Under various radiation dose levels, the deep learning model shows higher detectability indexes compared to FBP.

Tumor resectability and response on CT following neoadjuvant therapy for pancreatic cancer: inter-observer agreement study.

OBJECTIVES: First, to measure inter-observer agreement regarding tumor resectability and response, and second, to measure diagnostic performance in predicting negative resection margin, on re-staging CTs of patients who received neoadjuvant therapy for pancreatic cancer. METHODS: This retrospective study included patients who received neoadjuvant therapy for borderline resectable pancreatic cancer from 2017 to 2020. Six readers independently evaluated initial staging and re-staging CT images. They categorized the resectability on re-staging CT based on the NCCN guideline, and evaluated tumor response to neoadjuvant therapy according to our proposed criteria on a 5-grade scale. For inter-observer agreement, Gwet's agreement coefficients were used. A crossed random effect model was used to pool the sensitivity and specificity of six readers in predicting negative resection margin. RESULTS: Seventy-seven patients with the median age of 66 (59-70) were included. The pooled agreement for tumor resectability was 0.64 (95% CI, 0.56-0.71) for differentiating the three categories, and 0.84 (0.77-0.91) for differentiating resectable or borderline resectable cancer vs. unresectable cancer. Agreement for tumor response grade was 0.89 (0.85-0.92). The pooled sensitivity and specificity for predicting negative resection margin were 48% (43-52%) and 61% (57-64%), respectively, when only "resectable" on re-staging CT was considered as index test positive. When either "resectable"' or "borderline resectable" was considered as positive, the pooled sensitivity and specificity were 91% (89-94%) and 5% (4-6%), respectively. CONCLUSION: CT can be used reliably with a high inter-observer agreement in selecting candidates for surgery after neoadjuvant therapy of pancreatic cancer. KEY POINTS: • On CT following neoadjuvant therapy of pancreatic cancer, six readers showed high agreement in differentiating resectable or borderline resectable vs. unresectable cancer (Gwet's coefficient, 0.84). • Inter-observer agreement was also high for our proposed tumor response grade (Gwet's coefficient, 0.89). • Specificity was very low (5%) while sensitivity was high (91%) when either resectable or borderline resectable cancer on re-staging CT was considered as predictive of negative resection margin status.

PrEP uptake and delivery setting preferences among clients visiting six healthcare facilities in Eswatini.

Due to the high HIV incidence among the general population of Eswatini, pre-exposure prophylaxis (PrEP) for HIV-exposed individuals is recommended. However, little is known about PrEP uptake and preferences in PrEP delivery healthcare setting among the general population. We conducted a secondary analysis of a randomized trial that aimed to increase PrEP uptake. All clients eligible for PrEP in one of six public-sector healthcare facilities in Eswatini were included. PrEP uptake was stratified by initial reason for visit (e.g. outpatient). Preferences in PrEP delivery setting were collected among those clients who initiated PrEP. A total of 1782 clients had their HIV acquisition risk assessed. Of these, 72% (1277/1782) were considered at risk by healthcare providers and, among them, 40% (517/1277) initiated PrEP. Uptake was higher among clients visiting specifically to initiate PrEP (93%), followed by HIV testing visits (45.8%) and outpatient visits (40%). Among those who initiated PrEP, preferred delivery settings were outpatient services (31%), HIV testing services (26%), family planning (21%) and antenatal services (14%). Men or those at high risk of HIV acquisition were more likely to prefer HIV testing and outpatient services, while young women were more likely to visit and express a preference for antenatal and family planning services. Outpatient services and HIV testing services could be preferable choices for PrEP delivery integration, due to the high PrEP uptake and delivery setting preferences of the populations who use these services. Antenatal and family planning could also be considered with a view to targeting the youngest women.

RESUMEN: Debido a la alta incidencia del VIH entre la población general de Eswatini, se recomienda la profilaxis previa a la exposición (PrEP) para las personas expuestas al VIH. Sin embargo, se sabe poco sobre la aceptación de la PrEP y las preferencias en el ámbito de la atención sanitaria de la PrEP entre la población general. Se realizó un análisis secundario de un ensayo clínico que pretendía aumentar la aceptación de la PrEP. Se incluyó a todos los clientes elegibles para la PrEP en uno de los seis centros sanitarios del sector público de Eswatini. La aceptación de la PrEP se estratificó según el motivo inicial de la visita (por ejemplo, paciente externo). Se recogieron las preferencias en el entorno de administración de la PrEP entre aquellos clientes que iniciaron la PrEP. Se evaluó el riesgo de adquisición del VIH de un total de 1.782 clientes (de 2.238 contactados, el 80%). De ellos, el 72% (1277/1782) fueron considerados de riesgo por los profesionales sanitarios y, entre ellos, el 40% (517/1277) iniciaron la PrEP. El consumo fue mayor entre los clientes que acudieron específicamente para iniciar la PrEP (93%), seguido de las visitas para realizar la prueba del VIH (45,8%) y las visitas ambulatorias (40%). Entre los que iniciaron la PrEP, los entornos de prestación preferidos fueron los servicios ambulatorios (31%), los servicios de pruebas del VIH (26%), la planificación familiar (21%) y los servicios prenatales (14%). Los hombres o las personas con alto riesgo de contraer el VIH tenían más probabilidades de preferir las pruebas del VIH y los servicios ambulatorios, mientras que las mujeres jóvenes tenían más probabilidades de acudir a los servicios prenatales y de planificación familiar y expresar su preferencia por ellos. Los servicios ambulatorios y los servicios de pruebas del VIH podrían ser opciones preferibles para la integración de la entrega de la PrEP, debido a la alta aceptación de la PrEP y a las preferencias del entorno de entrega de las poblaciones que utilizan estos servicios. Los servicios prenatales y de planificación familiar también podrían considerarse con vistas a dirigirse a las mujeres más jóvenes.