Search

N. gonorrhoeae, which causes the sexually transmissible infection gonorrhoea, remains a significant public health threat globally, with challenges posed by increasing transmission and antimicrobial resistance (AMR). The COVID-19 pandemic introduced exceptional circumstances into communicable disease control, impacting the transmission of gonorrhoea and other infectious diseases. Through phylogenomic and phylodynamic analysis of 5881 N. gonorrhoeae genomes from Australia, we investigated N. gonorrhoeae transmission over five years, including a time period during the COVID-19 pandemic. Using a novel cgMLST-based genetic threshold, we demonstrate persistence of large N. gonorrhoeae genomic clusters over several years, with some persistent clusters associated with heterosexual transmission. We observed a decline in both N. gonorrhoeae transmission and genomic diversity during the COVID-19 pandemic, suggestive of an evolutionary bottleneck. The longitudinal, occult transmission of N. gonorrhoeae over many years further highlights the urgent need for improved diagnostic, treatment, and prevention strategies for gonorrhoea., (© 2024. The Author(s).)

Introduction: Social network-based testing approaches (SNAs) encourage individuals ("test promoters") to motivate sexual partners and/or those in their social networks to test for HIV. We conducted a systematic review to examine the effectiveness, acceptability and cost-effectiveness of SNA., Methods: We searched five databases from January 2010 to May 2023, and included studies that compared SNA with non-SNA. We used random-effects meta-analysis to combine effect estimates. Certainty was assessed using the GRADE approach., Results: We identified 47 studies. SNA may increase uptake of HIV testing compared to non-SNA (RR 2.04, 95% CI: 1.06-3.95, Low certainty). The proportion of first-time testers was probably higher among partners or social contacts of test promoters using SNA compared to non-SNA (RR 1.49, 95% CI: 1.22-1.81, Moderate certainty). The proportion of people who tested positive for HIV may be higher among partners or social contacts of test promoters using SNA compared to non-SNA (RR 1.84, 95% CI: 1.01-3.35, Low certainty). There were no reports of any adverse events or harms associated with SNA. Based on six cost-effectiveness studies, SNA was generally cheaper per person tested and per person diagnosed compared to non-SNA. Based on 23 qualitative studies, SNA is likely to be acceptable to a variety of populations., Discussion: Our review collated evidence for SNA to HIV testing covering the key populations and the general population who may benefit from HIV testing. We summarized evidence for the effectiveness, acceptability and cost-effectiveness of different models of SNA. While we did not identify an ideal model of SNA that could be immediately scaled up, for each setting and population targeted, we recommend various implementation considerations as our meta-analysis showed the effectiveness might differ due to factors which include the testing modality (i.e. use of HIV self-testing), type of test promoters, long or short duration of recruitment and use of financial incentives., Conclusions: Social network-based approaches may enhance HIV testing uptake, increase the proportion of first-time testers and those testing positive for HIV. Heterogeneity among studies highlights the need for context-specific adaptations, but the overall positive impact of SNA on HIV testing outcomes could support its integration into existing HIV testing services., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background: Gay and bisexual men (GBM) remain overrepresented among syphilis diagnoses in Australia and globally. The extent to which changes in sexual networks associated with HIV pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) may have influenced syphilis transmission among GBM at the population-level is poorly understood. We describe trends in syphilis testing and incidence among GBM in Australia over eleven years spanning widespread uptake of HIV PrEP and TasP., Methods: We analysed linked clinical data from GBM aged 16 years or older across a sentinel surveillance network in Australia from January 1, 2012, to December 31, 2022. Individuals with at least two clinic visits and with at least two syphilis tests during the observations period were included in testing and incidence analyses, respectively. Annual rates of testing and infectious syphilis incidence from 2012 to 2022 were disaggregated by HIV status and PrEP use (record of PrEP prescription; retrospectively categorised as ever or never-PrEP user). Cox regression explored associations between demographics, PrEP use and history of bacterial sexually transmissible infections (STIs) and infectious syphilis diagnosis., Findings: Among 129,278 GBM (mean age, 34.6 years [SD, 12.2]) included in testing rate analyses, 7.4% were living with HIV at entry and 31.1% were prescribed PrEP at least once during the study period. Overall syphilis testing rate was 114.0/100 person-years (py) and highest among GBM with HIV (168.4/100 py). Syphilis testing increased from 72.8/100 py to 151.8/100 py; driven largely by increases among ever-PrEP users. Among 94,710 GBM included in incidence analyses, there were 14,710 syphilis infections diagnosed over 451,560 person-years (incidence rate = 3.3/100 py). Syphilis incidence was highest among GBM with HIV (6.5/100 py), followed by ever-PrEP users (3.5/100 py) and never-PrEP users (1.4/100 py). From 2012 to 2022, syphilis incidence increased among ever-PrEP users from 1.3/100 py to 5.1/100 py, and fluctuated between 5.4/100 py and 6.6/100 py among GBM with HIV. In multivariable Cox regression, previous syphilis diagnosis (adjusted hazard ratio [aHR] = 1.98, 95% CI = 1.83-2.14), living with HIV (aHR = 1.83, 95% CI = 1.12-1.25) and recent (past 12 m) prescription of PrEP (aHR = 1.78, 95% CI = 1.61-1.97) were associated with syphilis diagnosis., Interpretation: Syphilis trends between GBM with HIV and GBM with evidence of PrEP use have converged over the past decade in Australia. Our findings recommend targeting emergent syphilis control strategies (e.g. doxycycline post-exposure prophylaxis) to GBM with prior syphilis diagnoses, using HIV PrEP or who are living with HIV., Funding: Australian Department of Health and Aged Care, National Health and Medical Research Council., Competing Interests: M.W.T. reports speakers’ honoraria, consultancy fees and investigator-initiated research grants from Gilead Sciences. R.G. has received research support funding from Cepheid and SpeeDx. M.E.H. reports investigator-initiated research grants from Gilead Sciences and Abbvie outside of the submitted work. M.A.S. reports investigator-initiated research grants from Gilead Sciences and Abbvie and consulting fees from Gilead Sciences outside of the submitted work. M.B. reports medical advisory boards and speakers’ honoraria from Gilead Sciences and ViiV Healthcare, and funding to attend scientific meetings from Gilead Sciences, investigator-initiated research grants from ViiV Healthcare. EPFC is supported by an Australian National Health and Medical Research Council (NHMRC) Emerging Leadership Investigator Grant (GNT1172873), and has received speakers’ honoraria from Gilead Sciences, MSD and CSL Seqirus. CKF is supported by an Australian NHMRC Leadership Investigator Grant (GNT1172900). VC received payment from Gilead Science for participation on advisory board. DO is CEO of Health Equity Matters, Australia's peak community HIV organization, for part of the period during which the research was undertaken. All other authors declare no conflicts of interest., (© 2024 The Author(s).)

Objectives: The saliva of individuals with oropharyngeal gonorrhoea can contain viable Neisseria gonorrhoeae. This study examined if using saliva as a lubricant for masturbation is a risk factor for urethral gonorrhoea among men who have sex with men (MSM)., Methods: In this cross-sectional study, MSM aged ≥18 years attending the Melbourne Sexual Health Centre between February 2021 and December 2023 were surveyed. Data were collected on sexual activities in the past 7 days, including receiving fellatio, condomless insertive anal sex, docking, and using saliva for masturbation. Multivariable logistic regression examined associations between these exposures and urethral gonorrhoea., Results: The median age of the 3114 men was 32 (IQR: 27-40), with 4.7% (n = 145) testing positive for urethral gonorrhoea. Urethral gonorrhoea was independently associated with an increasing number of partners for condomless insertive anal sex (P < 0.001). It was not significantly associated with receiving fellatio (P = 0.613), docking (P = 0.207), or using saliva for masturbation (P = 0.117). However, of the 110 men who only used saliva for masturbation, two (1.8%) had urethral gonorrhoea, and one (0.9%) had both urethral and oropharyngeal gonorrhoea., Conclusion: Condomless insertive anal sex is the leading risk factor for urethral gonorrhoea and not using saliva as a lubricant for masturbation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Continuity and coordination-of-care for childhood cancer survivors with multiple chronic conditions are understudied but critical for appropriate follow-up care., Methods: From April through June 2022, 800 Childhood Cancer Survivor Study participants with two or more chronic conditions (one or more severe/life-threatening/disabling) were emailed the "Patient Perceived Continuity-of-Care from Multiple Clinicians" survey. The survey asked about survivors' main (takes care of most health care) and coordinating (ensures follow-up) provider, produced three care-coordination summary scores (main provider, across multiple providers, patient-provider partnership), and included six discontinuity indicators (e.g., having to organize own care). Discontinuity (yes/no) was defined as poor care on one or more discontinuity item. Chi-square tests assessed associations between discontinuity and sociodemographics. Modified Poisson regression models estimated prevalence ratios (PRs) for discontinuity risk associated with the specialty and number of years seeing the main and coordinating provider, and PRs associated with better scores on the three care-coordination summary measures. Inverse probability weights adjusted for survey non-participation., Results: A total of 377 (47%) survivors responded (mean age 48 years, 68% female, 89% non-Hispanic White, 78% privately insured, 74% ≥college graduate); 147/373 (39%) reported discontinuity. Younger survivors were more likely to report discontinuity (chi-square p = .02). Seeing the main provider ≤3 years was associated with more prevalent discontinuity (PR; 95%CI) (1.17; 1.02-1.34 vs ≥ 10 years). Cancer specialist main providers were associated with less prevalent discontinuity (0.81; 0.66-0.99 vs. primary care). Better scores on all three care-coordination summary measures were associated with less prevalent discontinuity: main provider (0.73; 0.64-0.83), across multiple providers (0.81; 0.78-0.83), patient-provider partnership (0.85; 0.80-0.89)., Conclusions: Care discontinuity among childhood cancer survivors is prevalent and requires intervention., (© 2024 American Cancer Society.)

The Oncofertility Consortium Pediatric Initiative Network has published recommendations about the risks of infertility due to gonadotoxic therapy. We abstracted gonadotoxic therapies from central nervous system (CNS) Children's Oncology Group (COG) protocols between 2000 and 2022. We assigned them as unknown, minimal, significant, or high levels of increased risk for gonadal dysfunction/infertility. Seven of 11 CNS protocols placed patients at a high level of risk in at least one treatment arm. Males (7/11) were most commonly at a high level of risk, followed by pubertal females (6/11) and prepubertal females (5/11), highlighting the importance of pre-treatment counseling regarding fertility preservation interventions in this population., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background The patterns of sexually transmitted infections (STIs) in populations may be influenced by the sexual mixing within the population. We aimed to investigate the assortative sexual mixing pattern by bisexuality in male-male partnerships. Methods This was a retrospective repeated cross-sectional study of men with mostly regular male partners attending the Melbourne Sexual Health Centre between 2011 and 2019. Data on sexual practices, including their sexual practices, presence of other male/female sex partners and the gender of sexual partners in the previous 3 and 12months, were collected using computer-assisted self-interview. We calculated the proportion of male partnerships where at least one man in the partnership reported a female sex partner. Results A total of 2056 male-male partnerships (i.e. 4112 individuals) with a median age of 29 years (IQR 25 to 35) were included. Overall, in 94.4% (1941/2056) of male-male partnerships both men had male partners only; however, in 5.5% (113/2056) of partnerships, one man had both male and female partners, and in 0.1% (2/2056) partnerships, both men had both male and female partners. No assortative relationship was found on the sexual mixing by bisexuality in male-male partnerships due to the low assortativity coefficient (r =0.006, 95% CI: -0.004 to 0.016). Conclusion One in 20 male-male partnerships had at least one man who had both male and female partners within the preceding year. Individuals were not selective by bisexuality, suggesting that partnerships of bisexual individuals are mixed proportionately to the distribution of their characteristics. Still, these sexual mixing practices may affect STI transmission dynamics.

Objective: HIV pre-exposure prophylaxis (PrEP) became available in Victoria, Australia, in 2016. We examined non-occupational post-exposure prophylaxis (nPEP) usage among gay, bisexual and other men who have sex with men (MSM) before and after PrEP became available., Methods: We included MSM attending Melbourne Sexual Health Centre for nPEP between 2011 and 2021. We analysed three periods: the 'pre-PrEP' (01 Jan 2011 to 25 Jul 2016), 'PrEP before COVID-19' (26 Jul 2016 to 31 Dec 2019), and 'PrEP during COVID-19' (01 Jan 2020 to 31 Dec 2021)., Results: There were 222,978 consultations for MSM; 8292 (3.7%) were nPEP consultations. The proportion of nPEP consultations increased from 3.3% (3093/94263) in the pre-PrEP period to 4.3% (3843/89251) in the PrEP before COVID-19 period then dropped to 3.4% (1356/39464) during the COVID-19 period. Compared to Australian-born MSM, MSM born in Central/South America (adjusted odds ratio [aOR]: 1.75; 95% confidence interval [CI]: 1.27-2.40) had the highest odds of accessing nPEP, followed by Asian-born MSM (aOR: 1.47; 95% CI: 1.27-1.71) after adjusting for PrEP availability and COVID-19. Those newly arrived in Australia in ≤4 years had higher odds (aOR: 1.14; 95% CI: 1.05-1.22) of accessing nPEP than those living in Australia for >4 years., Conclusion: nPEP prescriptions declined with PrEP availability. Newly arrived overseas-born MSM who are unlikely to have access to subsidised PrEP have a higher demand of nPEP., Implications for Public Health: Increasing PrEP education and ensuring equal access is vital in the drive to reduce new HIV diagnoses., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The impact of adverse childhood experiences (ACE, e.g., abuse, neglect, and/or household dysfunction experienced before the age of 18) and resilience on risk for cardiovascular disease (CVD) has not previously been investigated in adult survivors of childhood cancer., Methods: We conducted a nested case-control study among long-term, adult-aged survivors of childhood cancer from the Childhood Cancer Survivor Study. Self-report questionnaires ascertained ACEs and resilience, and scores were compared between cases with serious/life-threatening CVD and controls without CVD matched on demographic and cardiotoxic treatment factors., Results: Among 95 cases and 261 controls, the mean ACE score was 1.4 for both groups; 53.4% of survivors endorsed ≥1 ACE. No association was observed between ACEs or resilience and CVD in adjusted models., Conclusions: ACEs and resilience do not appear to contribute to CVD risk for adult survivors of childhood cancer with cardiotoxic treatment exposures., Impact: Although not associated with CVD in this population, ACEs are associated with serious health issues in other populations. Therefore, future studies could investigate the effects of ACEs on other health outcomes affecting childhood cancer survivors., (©2024 American Association for Cancer Research.)

Objectives: Cervicitis is associated with important reproductive sequelae. Primary causes include chlamydia and gonorrhoea, but a known sexually transmitted infection (STI) is not identified in >50% of cases (i.e. STI-negative cervicitis). Bacterial vaginosis (BV) and specific BV-associated bacteria have also been associated with cervicitis, but data are limited. We investigated the association between STI-negative cervicitis and vaginal microbiota composition., Methods: This was a case-control sub-study of the OhMG study conducted at the Melbourne Sexual Health Centre. Cases were women with cervicitis who tested negative for STIs (STI-negative cervicitis, n = 64). Controls were STI-negative asymptomatic women attending for STI-screening (n = 128). The vaginal microbiota was characterised using 16S rRNA gene sequencing. Vaginal community state types were compared between cases and controls using logistic regression. Differential abundance analysis was performed to identify taxa associated with STI-negative cervicitis., Results: STI-negative cervicitis cases were more likely than controls to have a Lactobacillus-deficient non-optimal microbiota (adjusted-odds-ratio 2.55, 95% CI 1.18-5.50). Compared to controls, cases had increased abundance of four BV-associated bacteria (Gardnerella, Fannyhessea vaginae, Prevotella bivia, Dialister micraerophilus) and decreased abundance of optimal lactobacilli., Conclusions: We report a positive association between non-optimal vaginal microbiota composition and STI-negative cervicitis. Specific anaerobic BV-associated bacteria may represent infectious causes of cervicitis., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Melbourne Sexual Health Centre received funding from SpeeDx Pty Ltd (Australia) in support of the parent OhMG study. SMG has received consultancy fees from Merck for work unrelated to this manuscript. All other authors report no potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Adolescents and young adults (AYAs) with cancer are at risk of poor psychosocial outcomes. AYAs grew up with the internet and digital technology, and mobile Health (mHealth) psychosocial interventions have the potential to overcome care access barriers., Objective: This pilot randomized controlled trial (RCT) aimed to establish the feasibility, acceptability, and preliminary efficacy of a fully automated mobile app version of the Promoting Resilience in Stress Management intervention (mPRISM). Promoting Resilience in Stress Management is an evidence-based intervention developed in collaboration with AYAs, based on stress and coping theory, resilience theory, and evidence-based coping strategies. We hypothesized that mPRISM would be feasible, acceptable, and appropriate., Methods: This is a parallel, 2-arm, single-site pilot RCT with a waitlist control design. The study will recruit 80 AYAs with cancer from a clinic. Eligible AYAs are aged 12 to 25 years, within 12 months of a new cancer diagnosis, receiving chemotherapy or radiation therapy, speak, read, or write in English, and are cognitively able to participate in study procedures. Recruitment by clinical research coordinators will occur remotely by phone, video, or text. Participants will be randomized to psychosocial usual care (UC) alone or UC plus mPRISM for an 8-week intervention period, and will remain unblinded to study condition. Enrolled participants will complete surveys at baseline before randomization, 8 weeks, and 3-month follow-up. Using a waitlist design, the UC arm will receive mPRISM upon completion of 3-month follow-up surveys. Those in the UC arm will complete 2 additional measurement points at immediate posttreatment and 3 months later. The primary outcomes of interest are feasibility, defined as ≥60% enrollment and ≥70% retention (ie, percentage of participants who completed the study), and "feasibility, acceptability, and appropriateness" as defined by cut-off scores ≥4/5 on 3 brief validated implementation outcome measures (feasibility of implementation measure, acceptability of intervention measure [AIM], intervention appropriateness measure [IAM]). We will apply top-box scoring for the implementation measures. Exploratory outcomes of interest include patient-reported health-related quality of life, resilience, distress, anxiety, depression, pain, and sleep. We will conduct an intention-to-treat analysis to compare the outcomes of the mPRISM arm versus the control arm with covariate-adjusted regression models. We will summarize individual digital usage metrics using descriptive statistics., Results: Since September 2023, we have enrolled 20 participants and recruitment is ongoing., Conclusions: Although our previous work suggests AYAs with cancer are interested in mHealth psychosocial interventions, such interventions have not yet been sufficiently evaluated or implemented among AYA oncology patients. mPRISM may serve as a potential mHealth intervention to fill this gap. In this study, we will test the feasibility, acceptability, and preliminary efficacy of mPRISM. This work will inform future larger-scale RCTs powered for efficacy outcomes., Trial Registration: ClinicalTrials.gov NCT05842902; https://clinicaltrials.gov/study/NCT05842902., International Registered Report Identifier (irrid): DERR1-10.2196/57950., (©Nancy Lau, Tonya M Palermo, Chuan Zhou, Isabel Badillo, Shannon Hong, Homer Aalfs, Joyce P Yi-Frazier, Elizabeth McCauley, Eric J Chow, Bryan J Weiner, Dror Ben-Zeev, Abby R Rosenberg. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.07.2024.)

Neisseria gonorrhoeae infection (gonorrhoea) is a global public health challenge, causing substantial sexual and reproductive health consequences, such as infertility, pregnancy complications and increased acquisition or transmission of HIV. There is an urgency to controlling gonorrhoea because of increasing antimicrobial resistance to ceftriaxone, the last remaining treatment option, and the potential for gonorrhoea to become untreatable. No licensed gonococcal vaccine is available. Mounting observational evidence suggests that N. meningitidis serogroup B outer membrane vesicle-based vaccines may induce cross-protection against N. gonorrhoeae (estimated 30%-40% effectiveness using the 4CMenB vaccine). Clinical trials to determine the efficacy of the 4CMenB vaccine against N. gonorrhoeae are underway, as are Phase 1/2 studies of a new gonococcal-specific vaccine candidate. Ultimately, a gonococcal vaccine must be accessible, affordable and equitably dispensed, given that those most affected by gonorrhoea are also those who may be most disadvantaged in our societies, and most cases are in less-resourced settings. This vaccine value profile (VVP) provides a high level, holistic assessment of the current data to inform the potential public health, economic and societal value of pipeline vaccines. This was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations. All contributors have extensive expertise on various elements of the N. gonorrhoeae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using published data obtained from peer-reviewed journals or reports., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JJO reports financial support from the World Health Organization and Australian National Health and Medical Research Foundation. Some of the authors are present or former staff members of the World Health Organization. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Approximately 20-50% of adolescent and young adult-aged childhood cancer survivors (AYA-CCS) experience sexual dysfunction (SD), although this healthcare need is widely underrecognized. Previous research from both AYA-CCS patients and their providers report that SD needs are unaddressed despite patient desires for SD discussions to be incorporated as part of their care. Patients and providers agree that standardized use of a patient-reported outcome measure may facilitate SD discussions; an SD screening approach was developed with patient and provider input. This study will measure the effectiveness of a standardized SD screening intervention and assess implementation outcomes and multilevel barriers and facilitators to guide future research., Methods: This multi-site, mixed methods, type 1 effectiveness-implementation hybrid trial will be evaluated using a pre-post design (NCT05524610). The trial will enroll 86 AYA-CCS (ages 15-39) from two cancer centers in the United States. The SD intervention consists of core fundamental functions with a "menu" of intervention options to allow for flexibility in delivery and tailoring in variable contexts. Effectiveness of the intervention on facilitating SD communication will be measured through patient surveys and clinical data; multivariable logistic regression will be used for the binary outcome of self-reported SD screening, controlling for patient-level predictors. Implementation outcomes will be assessed using mixed methods (electronic health record abstraction, patient and provider surveys, and provider interviews. Quantitative and qualitative findings will be merged using a joint display to understand factors affecting intervention success., Implications: Identification and treatment of SD in AYA-CCS is an important and challenging quality of life concern. The type 1 hybrid design will facilitate rapid translation from research to practice by testing the effects of the intervention while simultaneously identifying multilevel barriers and facilitators to real-world implementation. This approach will inform future testing and dissemination of the SD screening intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Demedis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To maximise the benefits of HIV self-testing (HIVST), it is critical to support self-testers in the testing process and ensure that they access appropriate prevention and care. To summarise systems and tools supporting HIVST (hereafter, 'support systems') and categorise them for future analysis, we synthesised the global data on HIVST support systems and proposed a typology. We searched five databases for articles reporting on one or more HIVST support systems and included 314 publications from 224 studies. Across 189 studies, there were 539 reports of systems supporting HIVST use; while across 115 studies, there were 171 reports of systems supporting result interpretation. Most commonly, these were pictorial instructions, followed by in-person demonstrations and in-person assistance while self-testing or reading self-test results. Less commonly, virtual interventions were also identified, including online video conferencing and smartphone apps. Smartphone-based automated result readers have been used in the USA, China, and South Africa. Across 173 studies, there were 987 reports of systems supporting post-test linkage to care; most commonly, these were in-person referrals/counselling, written referrals, and phone helplines. In the USA, Bluetooth beacons have been trialled to monitor self-test use and facilitate follow-up. We found that, globally, HIVST support systems use a range of methods, including static media, virtual tools, and in-person engagement. In-person and printed approaches were more common than virtual tools. Other considerations, such as linguistic and cultural appropriateness, may also be important in the development of effective HIVST programs.

Background: Current clinical care for common bacterial STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG)) involves empiric antimicrobial therapy when clients are symptomatic, or if asymptomatic, waiting for laboratory testing and recall if indicated. Near-to-patient testing (NPT) can improve pathogen-specific prescribing and reduce unnecessary or inappropriate antibiotic use in treating sexually transmitted infections (STI) by providing same-day delivery of results and treatment., Methods: We compared the economic cost of NPT to current clinic practice for managing clients with suspected proctitis, non-gonococcal urethritis (NGU), or as an STI contact, from a health provider's perspective. With a microsimulation of 1000 clients, we calculated the cost per client tested and per STI- and pathogen- detected for each testing strategy. Sensitivity analyses were conducted to assess the robustness of the main outcomes. Costs are reported as Australian dollars (2023)., Results: In the standard care arm, cost per client tested for proctitis, NGU in men who have sex with men (MSM) and heterosexual men were the highest at $247.96 (95% Prediction Interval (PI): 246.77-249.15), $204.23 (95% PI: 202.70-205.75) and $195.01 (95% PI: 193.81-196.21) respectively. Comparatively, in the NPT arm, it costs $162.36 (95% PI: 161.43-163.28), $158.39 (95% PI: 157.62-159.15) and $149.17 (95% PI: 148.62-149.73), respectively. Using NPT resulted in cost savings of 34.52%, 22.45% and 23.51%, respectively. Among all the testing strategies, substantial difference in cost per client tested between the standard care arm and the NPT arm was observed for contacts of CT or NG, varying from 27.37% to 35.28%., Conclusion: We found that NPT is cost-saving compared with standard clinical care for individuals with STI symptoms and sexual contacts of CT, NG, and MG., Competing Interests: Declaration of Competing Interest CSB and CKF were supported by an Australian National Health and Medical Research Council Leadership Investigator Grant (GNT1173361 and GNT1172900, respectively). JJO and EPFC are supported by an Australian National Health and Medical Research Council Emerging Leadership Investigator Grant (GNT1193955 and GNT1172873). YZ is supported by an Australian Government Research Training Program (RTP) scholarship. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We examined combinations of nine sexual activities that occurred during a sex episode with a recent male partner among men who have sex with men (MSM) who attended an urban sexual health clinic from April-2017 to September-2017. We collected the following sexual activities: tongue-kissing, penises touching, using saliva during mutual masturbation, performed rimming, received rimming, performed fellatio, received fellatio, insertive anal sex, and receptive anal sex. During a single-sex episode, the most common combinations of sexual activities involved all nine activities (10.6%, 166/1542). We assessed the agreement between any two sexual activities that occurred together during a sex episode. Agreement was highest for receiving rimming and receptive anal sex ( kappa  = 0.40; 95% CI: 0.35, 0.45), and performing rimming and insertive anal sex ( kappa  = 0.38; 95% CI: 0.33, 0.42). Agreement was lowest for insertive anal sex and receiving fellatio ( kappa  = -0.01; 95% CI: -0.05, 0.03), and receptive anal sex and insertive anal sex ( kappa  = -0.08; 95% CI: -0.13, 0.03). The sexual activities that occur between men are correlated with one another and this will influence transmission between anatomical sites.

Purpose: Type 2 diabetes mellitus (T2D) is a prevalent long-term complication of treatment in survivors of childhood cancer, with marked racial/ethnic differences in burden. In this study, we investigated trans-ancestral genetic risks for treatment-related T2D., Patients and Methods: Leveraging whole-genome sequencing data from the St Jude Lifetime Cohort (N = 3,676, 304 clinically ascertained cases), we conducted ancestry-specific genome-wide association studies among survivors of African and European genetic ancestry (AFR and EUR, respectively) followed by trans-ancestry meta-analysis. Trans-/within-ancestry replication including data from the Childhood Cancer Survivor Study (N = 5,965) was required for prioritization. Three external general population T2D polygenic risk scores (PRSs) were assessed, including multiancestry PRSs. Treatment risk effect modification was evaluated for prioritized loci., Results: Four novel T2D risk loci showing trans-/within-ancestry replication evidence were identified, with three loci achieving genome-wide significance ( P < 5 × 10 -8 ). Among these, common variants at 5p15.2 ( LINC02112 ), 2p25.3 ( MYT1L ), and 19p12 ( ZNF492 ) showed evidence of modifying alkylating agent-related T2D risk in both ancestral groups, but showed disproportionately greater risk in AFR survivors (AFR odds ratios [ORs], 3.95-17.81; EUR ORs, 2.37-3.32). In survivor-specific RNA-sequencing data (N = 207), the 19p12 locus variant was associated with greater ZNF492 expression dysregulation after exposures to alkylators. Elevated T2D risks across ancestry groups were only observed with increasing values for multiancestry T2D PRSs and were especially increased among survivors treated with alkylators (top v bottom quintiles: OR AFR , 20.18; P = .023; OR EUR , 13.44; P = 1.3 × 10 -9 )., Conclusion: Our findings suggest therapy-related genetic risks contribute to the increased T2D burden among non-Hispanic Black childhood cancer survivors. Additional study of how therapy-related genetic susceptibility contributes to this disparity is needed.

The Victorian Government introduced a time-limited human papillomavirus (HPV) catch-up program for gay, bisexual, and other men who have sex with men (GBMSM) aged ≤ 26 years in 2017-2019. We conducted a retrospective observational study to examine the accuracy of the self-report of HPV vaccination status using computer-assisted self-interviewing versus their immunization history via electronic health records. We included GBMSM aged 23-30 years visiting the Melbourne Sexual Health Centre (MSHC) in 2020-2021 because they were age-eligible for the HPV catch-up program in Victoria, Australia. Individuals who were unsure about their vaccination status were categorized as 'unvaccinated'. Of the 1,786 eligible men, 1,665 men self-reported their HPV vaccination status: 48.8% ( n  = 812) vaccinated, 17.4% ( n  = 289) unvaccinated, and 33.9% ( n  = 564) unsure. Self-reported HPV vaccination had a sensitivity of 61.3% (95%CI: 58.3 to 64.2%; 661/1079), a specificity of 74.2% (95%CI: 70.5 to 77.7%; 435/586), a positive predictive value of 81.4% (95%CI: 78.6 to 84.0%; 661/812), a negative predictive value of 51.0% (95%CI: 47.6 to 54.4%; 435/853), and an accuracy of 52.6% (95%CI: 50.1 to 55.0%). Our results showed that only half of GBMSM know and report their HPV vaccination status correctly. Novel approaches such as digital vaccine passports may be useful for individuals to accurately report their vaccination status to guide accurate clinical decisions and management.

Purpose: Treatment strategies for osteosarcoma evolving between 1970 and 1999 improved 5-year survival and continue as standard of care today. This report evaluates the impact of these evolving therapies on long-term health outcomes., Methods: Five-year survivors of childhood osteosarcoma in CCSS treated from 1970 to 1999 were evaluated for late (>5 years from diagnosis) mortality, chronic health conditions (CHCs), and health status using piecewise-exponential and logistical models. Comparisons were made between survivors and siblings without cancer, and among survivors examining historical and current standard chemotherapies (e.g., methotrexate/doxorubicin/cisplatin [MAP] vs. others), specific chemotherapy agents and surgical approaches (amputation vs. limb salvage [LS]). Models were evaluated adjusting for attained age, sex, race, ethnicity, and age at diagnosis., Results: A total of 1257 survivors of osteosarcoma were followed on average for 24.4 years. Twenty-year all-cause late mortality was 13.3% (95% confidence interval [CI]: 11.7%-14.9%) overall and 11.7% (95% CI: 6.9%-16.5%) for the subset treated with MAP plus LS. Survivors were at higher risk of CHCs (rate ratio [RR] 3.7, 95% CI: 3.2-4.3) than the sibling cohort, most notably having more serious cardiac, musculoskeletal, and hearing CHCs. Within the survivor cohort, the risk of severe CHCs was twice as high with MAP versus no chemotherapy (RR 2.1, 95% CI: 1.3-3.4). Compared with primary amputation, serious musculoskeletal CHCs were higher after LS (RR 6.6, 95% CI: 3.6-13.4), without discernable differences in health status., Conclusion: Contemporary osteosarcoma therapy with MAP plus LS, while improving 5-year disease-free survival, continues to be associated with a high burden of late mortality, CHCs, and health status limitations., (© 2024 Wiley Periodicals LLC.)

Background: Interventions to increase physical activity are needed in adolescent and young adult survivors of childhood cancer who are largely inactive but at lifelong elevated risk of multiple chronic conditions improved by physical activity. The goals of the StepByStep study are to evaluate the effects of a 48-week distance-based, multi-component mobile health and social media behavioral intervention on physical activity, biomarkers of cardiometabolic health, and health-related quality of life., Methods: This ongoing study is a two-arm, prospective, multi-site randomized controlled trial. 384 childhood cancer survivors age ≥ 15 years and < 21 years who were 3-36 months off therapy and not meeting physical activity guidelines were enrolled. The trial will test the efficacy of a 24-week intensive multi-component physical activity intervention combining a wearable physical activity tracker, social media peer support group, and individualized goal setting followed by a 24-week maintenance phase of the intervention to improve outcomes. The control group receives the wearable physical activity tracker only., Conclusion: There is a growing need for novel, developmentally appropriate interventions to increase physical activity and improve the health trajectory of adolescent and young adult survivors of childhood cancer. If efficacious, this portable and scalable intervention would be a much-needed tool to reduce the morbidity from cancer treatment and improve quality of life among survivors after treatment ends., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04089358; COG Identifier: ALTE2031., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

While ceftriaxone remains the first-line treatment for gonorrhoea, the US CDC recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021-2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176) and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was the highest among women (16.4%, 10/61), followed by men-who-have-sex-with-women (6.4%, 7/109), and men-who-have-sex-with-men (5.8%, 57/982). The prevalence of cefixime-resistant N. gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; and thus, cefixime treatment would have limited benefits in Australia., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Sexual health clinics were frontline providers in the 2022 US mpox public health response, though data on clinic-based mpox vaccine scale-up, diagnoses, and treatment are limited. We describe the role of a public health sexual health clinic (SHC) in King County's mpox response, between 5/23/22-10/31/22., Methods: In July 2022, the SHC implemented a dedicated vaccine clinic and presumptive tecovirimat treatment (prior to laboratory confirmation) with on-site dispensation. We describe SHC's vaccine scale-up and contribution to clinical care by calculating the weekly number of vaccines administered by SHC and the total number of patients diagnosed and treated for mpox within SHC, and comparing to countywide data. We calculated time from symptom onset to testing and time from testing to treatment, and assessed temporal changes in these metrics using linear regression., Results: The SHC provided ≥1 vaccine doses to 7,442 individuals (10,295 doses), administering 42% of the 24,409 vaccine doses provided countywide, with the greatest contribution in the first week of August (n = 1,562, 58% of countywide vaccinations that week). Of 598 patients evaluated for mpox and tested, 178 (30%) tested positive (37% of countywide cases), and 152 (85% of SHC patients with mpox) received tecovirimat (46% of treatment countywide). Median time from symptom onset to testing decreased from 12 to 6 days (p = 0.045); time from testing to treatment decreased from 4.5 days to 0 days (p < 0.001)., Conclusion: The SHC was central to mpox vaccination and treatment scale-up, particularly in the first months of the 2022 epidemic., Competing Interests: Potential Conflicts of Interest: CST, KZ, SOH, NO, and SP have no conflicts of interest to disclose. ENK and EJC have received IDSA travel grants to attend ID week. CAC has received consultant fees from Roche Diagnostics. MRG has received research support from Hologic and SpeeDx. MSR received research funding from Nabriva unrelated to this work that has since ended. JCD has conducted research with donated supplies from Hologic and Mayne Pharmaceuticals., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia., Methods: A comprehensive collection of HIV-1 pol sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale., Findings: Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 pol sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers ( R e ) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low R e values., Interpretation: This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia., Funding: National Health and Medical Research Council, Australian Research Council., Competing Interests: Professor Sharon Lewin has received consulting fees from Abivax, Geovax, ViiV, Tetralogic, Vaxxinity, and Esfam, as well as honoraria from Gilead and Merck Sharpe & Dohme (Merck). The Victorian Department of Health co-funded this research and were involved project conception and data acquisition, although was not involved in the analysis or interpretation of results for this work. The authors declare no other conflicts., (© 2024 The Author(s).)

Background: Approximately 20-50% of adolescent and young adult-aged childhood cancer survivors (AYA-CCS) experience sexual dysfunction (SD), although this healthcare need is widely underrecognized. Previous research from both AYA-CCS patients and their providers report that SD needs are unaddressed despite patient desires for SD discussions to be incorporated as part of their care. Patients and providers agree that standardized use of a patient-reported outcome measure may facilitate SD discussions; an SD screening approach was developed with patient and provider input. This study will measure the effectiveness of a standardized SD screening intervention and assess implementation outcomes and multilevel barriers and facilitators to guide future research., Methods: This multi-site, mixed methods, type 1 effectiveness-implementation hybrid trial will be evaluated using a pre-post design (NCT05524610). The trial will enroll 86 AYA-CCS (ages 15-39) from two cancer centers in the United States. The SD intervention consists of core fundamental functions with a "menu" of intervention options to allow for flexibility in delivery and tailoring in variable contexts. Effectiveness of the intervention on facilitating SD communication will be measured through patient surveys and clinical data; multivariable logistic regression will be used for the binary outcome of self-reported SD screening, controlling for patient-level predictors. Implementation outcomes will be assessed using mixed methods (electronic health record abstraction, patient and provider surveys, and provider interviews. Quantitative and qualitative findings will be merged using a joint display to understand factors affecting intervention success., Implications: Identification and treatment of SD in AYA-CCS is an important and challenging quality of life concern. The type 1 hybrid design will facilitate rapid translation from research to practice by testing the effects of the intervention while simultaneously identifying multilevel barriers and facilitators to real-world implementation. This approach will inform future testing and dissemination of the SD screening intervention., Competing Interests: Declaration of Interests The authors have declared that no competing interests exist.

Introduction: Longitudinal data on how acute respiratory illness (ARI) affects behavior, namely school or work participation, and nonpharmaceutical intervention (NPI) usage before and during the COVID-19 pandemic is limited. The authors assessed how ARIs and specific symptoms affected school, work, and health-related behaviors over time., Methods: From November 2019 to June 2021, participating households with children in King County, Washington, were remotely monitored for ARI symptoms weekly. Following ARIs, participants reported illness-related effects on school, work, and NPI use. Using logistic regression with generalized estimating equations, the authors examined associations between symptoms and behaviors., Results: Of 1,861 participants, 581 (31%) from 293 households reported 884 ARIs and completed one-week follow-up surveys. Compared with the prepandemic period, during the period of the pandemic pre-COVID-19 vaccine, ARI-related school (56% vs 10%, p <0.001) absenteeism decreased and masking increased (3% vs 28%, p <0.001). After vaccine authorization in December 2020, more ARIs resulted in masking (3% vs 48%, p <0.001), avoiding contact with non-household members (26% vs 58%, p <0.001), and staying home (37% vs 69%, p <0.001) compared with the prepandemic period. Constitutional symptoms such as fever were associated with work disruptions (OR=1.91; 95% CI=1.06, 3.43), staying home (OR=1.55; 95% CI=1.06, 2.27), and decreased contact with non-household members (OR=1.58; 95% CI=1.05, 2.36)., Conclusions: This remote household study permitted uninterrupted tracking of behavioral changes in families with children before and during the COVID-19 pandemic, identifying increased use of some NPIs when ill but no additional illness-associated work or school disruptions., (© 2024 The Authors.)

Gene regulatory networks within cells modulate the expression of the genome in response to signals and changing environmental conditions. Reconstructions of gene regulatory networks can reveal the information processing and control principles used by cells to maintain homeostasis and execute cell-state transitions. Here, we introduce a computational framework, D-SPIN, that generates quantitative models of gene regulatory networks from single-cell mRNA-seq datasets collected across thousands of distinct perturbation conditions. D-SPIN models the cell as a collection of interacting gene-expression programs, and constructs a probabilistic model to infer regulatory interactions between gene-expression programs and external perturbations. Using large Perturb-seq and drug-response datasets, we demonstrate that D-SPIN models reveal the organization of cellular pathways, sub-functions of macromolecular complexes, and the logic of cellular regulation of transcription, translation, metabolism, and protein degradation in response to gene knockdown perturbations. D-SPIN can also be applied to dissect drug response mechanisms in heterogeneous cell populations, elucidating how combinations of immunomodulatory drugs can induce novel cell states through additive recruitment of gene expression programs. D-SPIN provides a computational framework for constructing interpretable models of gene-regulatory networks to reveal principles of cellular information processing and physiological control., Competing Interests: Declaration of Interests The work was supported in part by funds from a Caltech Amgen Research Collaboration Award and reagent gifts from 10x Genomics. MWT received funding from Adaptive Biotechnologies for unrelated work. MWT is a member of the advisory board of Cell Systems. MWT is a co-founder of CognitiveAI and YurtsAI. ZJG is a co-founder of Scribe Biosciences. The Regents of the University of California with ZJG and CSM as inventors have filed patent applications related to MULTI-seq.

Treatment for childhood solid tumors may lead to an increased risk for gonadal dysfunction/infertility. Discussion of risk should occur at diagnosis, any changes in therapy, and during survivorship. Gonadotoxic therapies were abstracted from 32 Children's Oncology Group (COG) phase III, frontline solid tumor protocols, in use from 2000 to 2022. Risk for gonadal dysfunction/infertility was assessed based on gonadotoxic therapies, sex, and pubertal status and assigned as minimal, significant, and high following the Oncofertility Consortium Pediatric Initiative Network (PIN) risk stratification. Most protocols (65.6%, 21/32) contained at least one therapeutic arm with a high level of increased risk. Solid tumor therapies present challenges in risk stratification due to response-adjusted therapy and the need to account for radiation field in the risk assessment. This guide hopes to serve as a tool to assist in standardizing gonadotoxic risk assessments across disciplines and improve referral for fertility services and reproductive health counseling for patients receiving COG-based solid tumor therapy. Internationally, many solid tumor therapies follow similar paradigms to COG studies, and risk stratifications may be generalizable to similar styles of therapy. In addition, this model may be applied to other international groups with the goal of standardizing fertility assessments., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: The risk factors for oropharyngeal gonorrhea have not been examined in sex workers despite the increasing prevalence of gonorrhea infection., Objective: This study aims to determine the risk factors for oropharyngeal gonorrhea in female and gender-diverse sex workers (including cisgender and transgender women, nonbinary and gender fluid sex workers, and those with a different identity) and examine kissing, oral sex, and mouthwash practices with clients., Methods: This mixed methods case-control study was conducted from 2018 to 2020 at 2 sexual health clinics in Melbourne, Victoria, and Sydney, New South Wales, Australia. We recruited 83 sex workers diagnosed with oropharyngeal gonorrhea (cases) and 581 sex workers without (controls). Semistructured interviews with 19 sex workers from Melbourne were conducted., Results: In the case-control study, the median age of 664 sex workers was 30 (IQR 25-36) years. Almost 30% of sex workers (192/664, 28.9%) reported performing condomless fellatio on clients. Performing condomless fellatio with clients was the only behavior associated with oropharyngeal gonorrhea (adjusted odds ratio 3.6, 95% CI 1.7-7.6; P=.001). Most participants (521/664, 78.5%) used mouthwash frequently. In the qualitative study, almost all sex workers reported kissing clients due to demand and generally reported following clients' lead with regard to kissing style and duration. However, they used condoms for fellatio because they considered it a risky practice for contracting sexually transmitted infections, unlike cunnilingus without a dental dam., Conclusions: Our study shows that condomless fellatio is a risk factor for oropharyngeal gonorrhea among sex workers despite most sex workers using condoms with their clients for fellatio. Novel interventions, particularly targeting the oropharynx, will be required for oropharyngeal gonorrhea prevention., (©Tiffany R Phillips, Christopher K Fairley, Kate Maddaford, Anna McNulty, Basil Donovan, Rebecca Guy, Ruthy McIver, Rebecca Wigan, Rick Varma, Jason J Ong, Denton Callander, Gabrielle Skelsey, Mish Pony, Dylan O'Hara, Jade E Bilardi, Eric PF Chow. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 20.05.2024.)

Background: Nontoxigenic Corynebacterium diphtheriae, often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae-positive cultures to determine if detections had increased over time and evaluated epidemiologic trends., Methods: We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification., Results: Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae-positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae-positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19., Conclusions: Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed., Competing Interests: Potential conflicts of interest. E. N. K. and E. J. C. received Infectious Diseases Society of America (IDSA) travel grants to attend ID Week. T. F. received a travel grant to attend the Conference on Retroviruses and Opportunistic Infections (CROI). H. N. K. is funded by the National Institute for Allergy and Infectious Diseases and Gilead, with funds paid directly to the institution, unrelated to this work. P. S. P. and E. J. C. received honoraria for teaching CME courses through Providence Health System, unrelated to this work. All other authors report no potential conflicts. All authors have completed the ICMJE conflict of interest forms. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Eric J. Chow reports receipt of a travel grant from the Infectious Diseases Society of America to attend IDWeek 2022 and honoraria from Providence Health & Services for presentations on COVID-19. No other potential conflicts of interest were disclosed.

Background: Achieving virtual elimination of HIV transmission in Australia requires a combination of high treatment rates and high testing coverage among individuals at risk of acquiring HIV. HIV self-testing (HIVST) is an additional testing approach for key populations., Objective: We aimed to examine the knowledge, attitudes, and practices of HIVST among Asian-born gay, bisexual and other men who have sex with men (GBMSM)., Methods: This qualitative study used semi-structured interviews of overseas-born GBMSM of Asian background in Australia. Participants were recruited from personal networks, social media platforms, snowballing, and the Melbourne Sexual Health Centre. Twenty-five participants were purposively sampled with a range of ages and previous levels of experience with HIVST. Interview transcripts were imported into Nvivo 12 for data management., Results: The age of the participants ranged from 19 to 44 years, with a median of 30 years. Most were unaware of HIVST before the interview, and only a few had ever used one. All had limited sexual health knowledge (i.e., HIV testing, PrEP) before they arrived in Australia. Upon learning about HIVST during the interview, many expressed willingness to use HIVST, but in limited circumstances, such as traveling overseas, interim testing while taking on-demand PrEP, and point-of-sex testing. Almost all were open to distributing HIVST to their casual partners or friends, especially those they knew who engaged in high-risk sexual practice (i.e., condomless anal sex) and were not engaged in sexual healthcare. About half still preferred conventional serology testing because of regular HIV testing as part of PrEP prescription and the need for testing for other sexually transmitted infections., Conclusion: HIVST may be an acceptable additional testing approach for HIV testing among Asian-born GBMSM. Peer education and secondary distribution may help raise HIVST awareness and use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zhang, Chow, Sudarto, Wang, Stoove, Medland, O'Donnell, Keen, Ong and Phillips.)

Background: How often mpox causes asymptomatic infections, particularly among persons who have received the Modified Vaccinia Ankara (MVA) vaccine, is unknown., Methods: We performed mpox polymerase chain reaction testing on rectal and pharyngeal specimens collected from symptomatic and asymptomatic patients at a sexual health clinic in Seattle, WA, between May 2022 and May 2023. Analyses evaluated the prevalence of asymptomatic or subclinical infection and, among persons with polymerase chain reaction-positive tests, the association of MVA vaccination status with the symptomatic infection., Results: The study population included 1663 persons tested for mpox during 2353 clinic visits. Ninety-three percent of study participants were cisgender men and 96% were men who have sex with men. A total of 198 symptomatic patients (30%) had a first mpox-positive test during 664 visits. Eighteen patients (1.1%) tested during 1689 visits had asymptomatic or subclinical mpox based on a positive rectal or pharyngeal test done in the absence of testing done because of clinical suspicion for mpox. Fourteen (78%) of 18 persons with asymptomatic/subclinical mpox and 53 (26%) of 198 persons with symptomatic mpox had received at least 1 dose of the MVA vaccine ( P < 0.0001). Controlling for calendar month, study subjects who received 1 and 2 doses of MVA vaccine were 4.4 (95% confidence interval, 1.3-15) and 11.9 (3.6-40) times more likely to have asymptomatic versus symptomatic mpox, respectively, than persons who were unvaccinated., Conclusions: Asymptomatic mpox is uncommon. Modified Vaccinia Ankara vaccination is associated with an asymptomatic/subclinical infection among persons with mpox., Competing Interests: Conflict of Interest and Sources of Funding: M.R.G., and O.O.S. P.S., have received research support from Hologic and SpeeDx. C.C. has been a paid consultant to Roche Diagnostics. M.R. has received research support from Nabriva. J.C.D. has received research support from Hologic and Mayne Pharmaceuticals. A.L.G. has done contract laboratory testing for Abbott, Cepheid, Novavax, Pfizer, Janssen, and Hologic, and has received research support from Gilead. E.J.C., E.N.K., M.M., J.P.G., and A.B. have no conflicts of interest. None of the listed conflicts of interest relate to mpox or the work presented in this manuscript., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Importance: Employment is an important factor in quality of life and provides social and economic support. Longitudinal data on employment and associations with chronic health conditions for adult survivors of childhood cancer are lacking., Objective: To evaluate longitudinal trends in employment among survivors of childhood cancer., Design, Setting, and Participants: Retrospective cohort study of 5-year cancer survivors diagnosed at age 20 years or younger between 1970 and 1986 enrolled in the multi-institutional Childhood Cancer Survivor Study (CCSS). Sex-stratified employment status at baseline (2002 to 2004) and follow-up (2014 to 2016) was compared with general population rates from the Behavioral Risk Factor Surveillance System cohort. Data were analyzed from July 2021 to June 2022., Exposures: Cancer therapy and preexisting and newly developed chronic health conditions., Main Outcomes and Measures: Standardized prevalence ratios of employment (full-time or part-time, health-related unemployment, unemployed, not in labor force) among adult (aged ≥25 years) survivors between baseline and follow-up compared with the general population. Longitudinal assessment of negative employment transitions (full-time to part-time or unemployed at follow-up)., Results: Female participants (3076 participants at baseline; 2852 at follow-up) were a median (range) age of 33 (25-53) years at baseline and 42 (27-65) years at follow-up; male participants (3196 participants at baseline; 2557 at follow-up) were 33 (25-54) and 43 (28-64) years, respectively. The prevalence of full-time or part-time employment at baseline and follow-up was 2215 of 3076 (71.3%) and 1933 of 2852 (64.8%) for female participants and 2753 of 3196 (85.3%) and 2079 of 2557 (77.3%) for male participants, respectively, with declining standardized prevalence ratios over time (female participant baseline, 1.01; 95% CI, 0.98-1.03; follow-up, 0.94; 95% CI, 0.90-0.98; P < .001; male participant baseline, 0.96; 95% CI, 0.94-0.97; follow-up, 0.92; 95% CI, 0.89-0.95; P = .02). While the prevalence of health-related unemployment increased (female participants, 11.6% to 17.2%; male participants, 8.1% to 17.1%), the standardized prevalence ratio remained higher than the general population and declined over time (female participant baseline, 3.78; 95% CI, 3.37-4.23; follow-up, 2.23; 95% CI, 1.97-2.51; P < .001; male participant baseline, 3.12; 95% CI, 2.71-3.60; follow-up, 2.61; 95% CI, 2.24-3.03; P = .002). Among survivors employed full-time at baseline (1488 female participants; 1933 male participants), 285 female participants (19.2%) and 248 male participants (12.8%) experienced a negative employment transition (median [range] follow-up, 11.5 [9.4-13.8] years). Higher numbers and grades of chronic health conditions were significantly associated with these transitions., Conclusions and Relevance: In this retrospective analysis of adult survivors of childhood cancer, significant declines in employment and increases in health-related unemployment among cancer survivors compared with the general population were identified. A substantial portion of survivors in the midcareer age range fell out of the workforce. Awareness among clinicians, caregivers, and employers may facilitate clinical counseling and occupational provisions for supportive work accommodations.

Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L23-0449.

Background: Asian-born MSM are a priority population as Australia aims to end HIV transmission, but they reported additional barriers to access PrEP and other HIV prevention methods. This study investigates factors associated with PrEP use among Asian MSM in Sydney and Melbourne, Australia, to inform strategies to improve PrEP uptake in this population., Methods: This was a sub-analysis of a community-based cross-sectional survey conducted from March to June 2021. We recruited participants online in Sydney and Melbourne, Australia. Univariable and multivariable logistic regression analyses were performed to identify the factors associated with PrEP use in the last six months and lifetime. Latent class analyses were used to identify subgroups of Asian MSM sharing similar characteristics related to their risk practices for HIV., Findings: Overall, 870 Asian MSM were included: 288 Oceanian-born Asian MSM and 582 Asian-born MSM. Three latent classes were identified: 1) Asian-born MSM who recently arrived in Australia with limited English, were less likely to use PrEP and at higher risk of HIV infection (e.g., had condomless anal sex with a casual sex partner in the last six months) (4.6%); 2) Asian MSM who were at lower risk of HIV infection and less likely to use PrEP (69.3%) and; 3) Asian MSM who were at substantial risk of HIV infection and more likely to use PrEP (26.1%). Compared to Oceanian-born Asian MSM, those who were born in Southeast Asia (adjusted odds ratio (aOR) = 0.5, 95% confidence interval (CI) 0.3-0.7) and South Asia (aOR = 0.4, 95% CI 0.2-0.8) were less likely to ever use PrEP. Compared to Oceanian-born Asian MSM, those who were born in Southeast Asia (aOR = 0.4, 95% CI 0.3-0.7), Northeast Asia (aOR = 0.5, 95% CI 0.3-0.8) and South Asia (aOR = 0.4, 95% CI 0.2-0.7) were less likely to use PrEP in the last six months., Interpretation: To end HIV transmission in Australia, it will be necessary to develop strategies to improve PrEP access for the significant minority of Asian-born MSM who are at substantial risk of HIV infection., Funding: EPFC and JJO are supported by an Australian National Health and Medical Research Council (NHMRC) Emerging Leadership Investigator Grant (EPFC: GNT1172873 and JJO: GNT1193955). CKF is supported by an Australian National Health and Medical Research Council (NHMRC) Leadership Investigator Grant (GNT1172900)., Competing Interests: No authors reported conflict of interest., (© 2024 The Author(s).)

Introduction: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae , has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis , may provide cross-protection against the closely related bacterium N. gonorrhoeae . This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+)., Methods and Analysis: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm 3 ), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae -specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae -specific antibodies., Ethics and Dissemination: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences., Trial Registration Number: NCT04415424., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Denosumab is a fully human mAb that binds receptor activator of NFκB ligand (RANKL). It is routinely administered to patients with cancer to reduce the incidence of new bone metastasis. RANK-RANKL interactions regulate bone turnover by controlling osteoclast recruitment, development, and activity. However, these interactions also can regulate immune cells including dendritic cells and medullary thymic epithelial cells. Inhibition of the latter results in reduced thymic negative selection of T cells and could enhance the generation of tumor-specific T cells. We examined whether administering denosumab could modify modulate circulating immune cells in patients with cancer. Blood was collected from 23 patients with prostate cancer and 3 patients with renal cell carcinoma, all of whom had advanced disease and were receiving denosumab, prior to and during denosumab treatment. Using high-dimensional mass cytometry, we found that denosumab treatment by itself induced modest effects on circulating immune cell frequency and activation. We also found minimal changes in the circulating T-cell repertoire and the frequency of new thymic emigrants with denosumab treatment. However, when we stratified patients by whether they were receiving chemotherapy and/or steroids, patients receiving these concomitant treatments showed significantly greater immune modulation, including an increase in the frequency of natural killer cells early and classical monocytes later. We also saw broad induction of CTLA-4 and TIM3 expression in circulating lymphocytes and some monocyte populations. These findings suggest that denosumab treatment by itself has modest immunomodulatory effects, but when combined with conventional cancer treatments, can lead to the induction of immunologic checkpoints. See related Spotlight by Nasrollahi and Davar, p. 383., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Sexual function (SF) concerns are common among adolescent and young adult (AYA) cancer survivors, are underrecognized and undertreated. This study sought AYA oncology provider input on the implementation of an SF screening tool to address this unmet need., Procedure: Semi-structured interviews were completed with oncology providers (n = 25) who care for AYAs at a single institution. Interviews sought to understand barriers to addressing SF, elicit perspectives on use of an established screening tool, and obtain recommendations for SF screening intervention development and implementation. Interviews were developed using the Consolidated Framework for Implementation Research (CFIR); thematic analysis-guided interpretation., Results: AYA oncology providers were in favor of using an SF screening tool, but confirmed previously identified barriers and implementation considerations within multiple CFIR domains, including concerns about privacy, patient comfort, provider buy-in, provider knowledge, resource needs, and workflow/capacity constraints. They identified numerous strategies to address barriers through screening intervention design and implementation approaches. For example, provider buy-in could be optimized through education, availability of clinical resources, creation of a dedicated sexual healthcare team, provider engagement in intervention development, and leadership involvement., Conclusions: Development and implementation of an effective SF screening intervention is necessary to improve diagnosis and treatment of sexual dysfunction, with the ultimate goal of improving sexual health-related quality of life in AYA cancer survivors. AYA oncology providers identified numerous intervention and implementation design strategies for the development and implementation of an SF screening intervention, which must be integrated with patient recommendations., (© 2024 Wiley Periodicals LLC.)

Background: Siblings of children with cancer may experience adverse household economic consequences, but their financial outcomes in adulthood are unknown., Methods: A total of 880 siblings (aged 18-64 years) of adult-aged childhood cancer survivors were surveyed to estimate the prevalence of financial hardship by three established domains (behavioral, material, and psychological). For individual financial hardship items matching the contemporaneous National Health Interview Survey or Behavioral Risk Factor Surveillance System, siblings were compared with the general population by calculating adjusted prevalence odds ratios (ORs) to sample-weighted responses. Multivariable logistic regression models examined associations between sibling characteristics and each hardship domain and between sibling hardship and survivors' cancer/treatment characteristics., Results: Behavioral, material, and psychological hardship was reported by 24%, 35%, and 28%, respectively. Compared with national survey respondents, siblings were more likely to report worries about medical bills (OR, 1.14; 95% confidence interval [CI], 1.06-1.22), difficulty affording nutritious foods (OR, 1.79; 95% CI, 1.54-2.07), and forgoing needed medical care (OR, 1.38; 95% CI, 1.10-1.73), prescription medications (OR, 2.52; 95% CI, 1.99-3.20), and dental care (OR, 1.34; 95% CI, 1.15-1.57) because of cost. Sibling characteristics associated with reporting financial hardship in one or more domains included female sex, older age, chronic health conditions, lower income, not having health insurance, high out-of-pocket medical expenditures, and nonmedical/nonhome debt. No survivor cancer/treatment characteristics were associated with sibling financial hardship., Conclusions: Adult siblings of childhood cancer survivors were more likely to experience financial hardship compared with the general population. Childhood cancer may adversely affect entire households, with potentially lasting implications., (© 2023 American Cancer Society.)

Background The incidence of sexual assault continues to rise in Australia. This study aimed to describe the nature of assault, HIV/STI positivity, and its management at a sexual health clinic. Methods We performed a chart review of 516 sexual assault cases presenting to Melbourne Sexual Health Centre between 2012 and 2021, collecting data on victim demographics, details of assault, HIV/STI testing and positivity, police involvement, and offer of counselling. Results We included 516 cases: 124 males (24.0%); 384 females (74.4%); and eight transgender (1.6%) victims. The proportion of assault cases presenting to Melbourne Sexual Health Centre increased from 0.1% (37/37,070) in 2012 to 0.2% (56/36,514) in 2021 (P trend =0.006). HIV post-exposure prophylaxis was prescribed for 64.5% (80/124) of males and 12.5% (48/384) of females. Among victims, 69.4% (358/516) were tested for HIV and no one tested positive, while 71.9% (371/516) were tested for syphilis, with 1.6% (6/371) positive. Gonorrhoea and chlamydia were tested at the oropharynx (44.8% [231/516] vs 28.7% [148/516]), genitals (83.7% [432/516] vs 92.4% [477/516]) and anorectum (35.3% [182/516] vs 35.3% [182/516]). Positivity for gonorrhoea and chlamydia were: 2.6% (6/231) vs 2.0% (3/148) at oropharynx, 1.4% (6/432) vs 2.9% (14/477) at genitals, and 5.5% (10/182) vs 7.1% (13/182) at anorectum. According to clinical records, 25.2% (130/516) of victims sought police involvement, and 71.7% (370/516) were offered counselling. Conclusions Sexual assault was an uncommon presentation at Melbourne Sexual Health Centre, with diverse circumstances surrounding assault; however, clinical documentation varied, indicating a need for a standard primary care protocol for clients presenting with acute sexual assault.

Background: Early during the COVID-19 pandemic, it was important to better understand transmission dynamics of SARS-CoV-2, the virus that causes COVID-19. Household contacts of infected individuals are particularly at risk for infection, but delays in contact tracing, delays in testing contacts, and isolation and quarantine posed challenges to accurately capturing secondary household cases., Methods: In this study, 346 households in the Seattle region were provided with respiratory specimen collection kits and remotely monitored using web-based surveys for respiratory illness symptoms weekly between October 1, 2020, and June 20, 2021. Symptomatic participants collected respiratory specimens at symptom onset and mailed specimens to the central laboratory in Seattle. Specimens were tested for SARS-CoV-2 using RT-PCR with whole genome sequencing attempted when positive. SARS-CoV-2-infected individuals were notified, and their household contacts submitted specimens every 2 days for 14 days., Results: In total, 1371 participants collected 2029 specimens that were tested; 16 individuals (1.2%) within 6 households tested positive for SARS-CoV-2 during the study period. Full genome sequences were generated from 11 individuals within 4 households. Very little genetic variation was found among SARS-CoV-2 viruses sequenced from different individuals in the same household, supporting transmission within the household., Conclusions: This study indicates web-based surveillance of respiratory symptoms, combined with rapid and longitudinal specimen collection and remote contact tracing, provides a viable strategy to monitor households and detect household transmission of SARS-CoV-2., Trial Registration Identifier: NCT04141930, Date of registration 28/10/2019., (© 2024. The Author(s).)

Background: Adult survivors of childhood cancer are at risk for cardiovascular events., Objectives: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations., Methods: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Cox proportional hazard regression models were used to estimate HRs and 95% CIs between groups, adjusted for demographic and clinical factors., Results: Among 25,658 childhood cancer survivors (median age at diagnosis 7 years, median age at follow-up or death 38 years) and 5,051 siblings, 1,780 survivors and 91 siblings had a cardiovascular event. After HF, CAD, and stroke, 10-year all-cause mortalities were 30% (95% CI: 26%-33%), 36% (95% CI: 31%-40%), and 29% (95% CI: 24%-33%), respectively, among survivors vs 14% (95% CI: 0%-25%), 14% (95% CI: 2%-25%), and 4% (95% CI: 0%-11%) among siblings. All-cause mortality risks among childhood cancer survivors were increased after HF (HR: 7.32; 95% CI: 2.56-20.89), CAD (HR: 5.54; 95% CI: 2.37-12.93), and stroke (HR: 3.57; 95% CI: 1.12-11.37). CAD-specific mortality risk was increased (HR: 3.70; 95% CI: 1.05-13.02). Among 5,114 CARDIA participants, 345 had a major event. Although CARDIA participants were on average decades older at events (median age 57 years vs 31 years), mortality risks were similar, except that all-cause mortality after CAD was significantly increased among childhood cancer survivors (HR: 1.85; 95% CI: 1.16-2.95)., Conclusions: Survivors of childhood cancer represent a population at high risk for mortality after major cardiovascular events., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Cancer Institute (CA55727, G.T.A. Principal Investigator; CA204378, E.J.C. Principal Investigator). Support to St Jude Children’s Research Hospital also provided by the Cancer Center Support (CORE) grant (CA21765, C. Roberts, Principal Investigator) and the American Lebanese-Syrian Associated Charities. Dr Bottinor is supported by To-morrow’s Research Fund St Baldrick’s Scholar Award (636214), the American Heart Association (19CDA34760181), and Clinical and Translational Science Award KL2TR002648 from the National Center for Advancing Translational Sciences. Dr Im is supported by the National Cancer Institute (R21 CA261833, C.I./Y. Yuan, Principal Investigators), the Children’s Cancer Research Fund, and the University of Minnesota Pediatric Foundation. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, and HHSN268201800007I from the National Heart, Lung, and Blood Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or sponsors. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In health-science research, outcomes ascertained through surveys and interviews are subject to potential bias with respect to the true outcome status, which is only ascertainable with clinical and laboratory assessment. This measurement error may lead to biased inference when evaluating associations between exposures and outcomes of interest. Here, we consider a cohort study in which the outcome of interest is ascertained via questionnaire, subject to imperfect ascertainment, but where a subset of participants also have a clinically assessed, validated outcome available. This presents a methodological opportunity to address potential bias. Specifically, we constructed the likelihood in two parts, one using the validated subset and the other using a subset without validation. This work expands on that proposed by Pepe and enables inference with standard statistical software. Weighted generalized linear model estimates for our method and maximum likelihood estimates (MLE) for Pepe's method were computed, and the statistical inference was based on the standard large-sample likelihood theory. We compare the finite sample performance of two approaches through Monte Carlo simulations. This methodological work was motivated by a large cohort study of long-term childhood cancer survivors, allowing us to provide a relevant application example where we examined the association between clinical factors and chronic health conditions., (© 2023 John Wiley & Sons Ltd.)

The growing community of childhood cancer survivors faces a heavy burden of late onset morbidities and mortality, with cardiovascular diseases being the leading noncancer cause. In addition to demographics and cancer treatment exposures, which cannot be altered, cardiometabolic risk factors (obesity, hypertension, diabetes, and dyslipidemia) and frailty potentiate the risk of morbidity and mortality associated with chronic health conditions. Important opportunities exist to target these risk factors and improve late health outcomes for survivors. Unfortunately, limited evidence exists on the optimal methods to prevent, screen, and treat cardiometabolic risk factors among survivors, resulting in significant underdiagnosis and undertreatment. In this review, we discuss the prevalence of, risk factors for, current survivor-specific recommendations, and gaps in knowledge to mitigate potentially modifiable cardiometabolic risk factors and frailty among survivors of childhood cancer., Competing Interests: This work was supported by funding from the American Lebanese Syrian Associated Charities and the Cancer Center Development Funds (CA021765) from the National Institute of Health. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: The epidemiology of respiratory viral infections is complex. How infection with one respiratory virus affects risk of subsequent infection with the same or another respiratory virus is not well described., Methods: From October 2019 to June 2021, enrolled households completed active surveillance for acute respiratory illness (ARI), and participants with ARI self-collected nasal swab specimens; after April 2020, participants with ARI or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and their household members self-collected nasal swab specimens. Specimens were tested using multiplex reverse-transcription polymerase chain reaction for respiratory viruses. A Cox regression model with a time-dependent covariate examined risk of subsequent detections following a specific primary viral detection., Results: Rhinovirus was the most frequently detected pathogen in study specimens (406 [9.5%]). Among 51 participants with multiple viral detections, rhinovirus to seasonal coronavirus (8 [14.8%]) was the most common viral detection pairing. Relative to no primary detection, there was a 1.03-2.06-fold increase in risk of subsequent virus detection in the 90 days after primary detection; risk varied by primary virus: human parainfluenza virus, rhinovirus, and respiratory syncytial virus were statistically significant., Conclusions: Primary virus detection was associated with higher risk of subsequent virus detection within the first 90 days after primary detection., Competing Interests: Potential conflicts of interest . E. J. C. received honoraria from Providence Regional Medical Center in Everett, Washington, for presentations on coronavirus disease 2019 and received a travel award from the Infectious Diseases Society of America to attend IDWeek 2022. J. A. E. reports consulting with AstraZeneca, Meissa Vaccines, and Sanofi Pasteur, as well as research support from AstraZeneca, GlaxoSmithKline, Merck, and Pfizer. H. Y. C. reports consulting with Ellume, Pfizer, the Bill and Melinda Gates Foundation, Glaxo Smith Kline, and Merck. She has received research funding from Gates Ventures and Sanofi Pasteur and support and reagents from Ellume and Cepheid, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: The rise in antimicrobial resistance in several STI pathogens such as Neisseria gonorrhoeae has become a public health threat as only one first-line treatment remains. Reducing screening interval for gonorrhoea and chlamydia in high-prevalence populations has been proposed to address antimicrobial stewardship, but this remains controversial. This review aimed to revisit the epidemiology of infections at the oropharynx and review the current screening recommendations and treatment guidelines in different populations., Recent Findings: Emerging evidence suggests that the oropharynx is the primary anatomical site for gonorrhoea transmission but maybe not for chlamydia transmission. Most international guidelines recommend 3-monthly oropharyngeal gonorrhoea and chlamydia screening for high-prevalence populations (e.g. men who have sex with men) but not low-prevalence populations (e.g. heterosexuals) given the clinical and public health benefits of screening in low-prevalence populations are still unclear. Doxycycline remains the first-line treatment for oropharyngeal chlamydia in most guidelines. However, some countries have moved from dual therapy (ceftriaxone and azithromycin) to monotherapy (ceftriaxone) for oropharyngeal gonorrhoea treatment to address antimicrobial stewardship., Summary: The transmission of gonorrhoea and chlamydia is still not fully understood. Further work will be required to evaluate the benefits and harms of reducing screening in high-prevalence populations., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chlamydia remains the most notified bacterial sexually transmissible infection in Australia with guidelines recommending testing for re-infection at 3months post treatment. This paper aimed to determine chlamydia retesting and repeat positivity rates within 2-4months among young women in Australia, and to evaluate what factors increase or decrease the likelihood of retesting., Methods: Chlamydia retesting rates among 16-29-year-old women were analysed from Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of sexually transmissible infection and bloodborne virus (ACCESS) sentinel surveillance data (n =62 sites). Among women with at least one positive test between 1 January 2018 and 31 August 2022, retesting counts and proportions within 2-4months were calculated. Logistic regression was performed to assess factors associated with retesting within 2-4months., Results: Among 8758 women who were positive before 31 August 2022 to allow time for follow up, 1423 (16.2%) were retested within 2-4months, of whom 179 (12.6%) tested positive. The odds of retesting within 2-4months were 25% lower if tested in a coronavirus disease 2019 (COVID-9) pandemic year (2020-2022) (aOR=0.75; 95% CI 0.59-0.95). Among 9140 women with a positive test before 30 November 2022, 397 (4.3%) were retested too early (within 7days to 1month) and 81 (20.4%) of those were positive., Conclusions: Chlamydia retesting rates remain low with around a sixth of women retested within 2-4months in line with guidelines. Re-infection is common with around one in eight retesting positive. An increase in retesting is required to reduce the risk of reproductive complications and onward transmission.

Background: A previous multicenter study showed that longitudinal changes in standard cardiac functional parameters were associated with the development of cardiomyopathy in childhood cancer survivors (CCS). Evaluation of the relationship between global longitudinal strain (GLS) changes and cardiomyopathy risk was limited, largely due to lack of quality apical 2- and 3-chamber views in addition to 4-chamber view. We sought to determine whether apical 4-chamber longitudinal strain (A4LS) alone can serve as a suitable surrogate for GLS in this population., Methods: A4LS and GLS were measured in echocardiograms with acceptable apical 2-, 3-, and 4-chamber views. Correlation was evaluated using Pearson and Spearman coefficients, and agreement was evaluated with Bland-Altman plots. The ability of A4LS to identify normal and abnormal values compared to GLS as the reference was evaluated., Results: Among a total of 632 reviewed echocardiograms, we identified 130 echocardiograms from 56 patients with adequate views (38% female; mean age at cancer diagnosis 8.3 years; mean follow-up 9.4 years). Correlation coefficients between A4LS and GLS were .89 (Pearson) and .85 (Spearman), with Bland-Altman plot of GLS-A4LS showing a mean difference of -.71 ± 1.8. Compared with GLS as the gold standard, A4LS had a sensitivity of 86% (95% CI 79%-93%) and specificity of 82% (69%-95%) when using normal range cutoffs and 90% (82%-97%) and 70% (58%-81%) when using ±2 standard deviations., Conclusion: A4LS performs well when compared with GLS in this population. Given the more recent adoption of apical 2- and 3-chamber views in most pediatric echocardiography laboratories, A4LS is a reasonable stand-alone measurement in retrospective analyses of older study cohorts and echocardiogram biorepositories., (© 2024 Wiley Periodicals LLC.)