Building a machine learning-assisted echocardiography prediction tool for children at risk for cancer therapy-related cardiomyopathy.

BACKGROUND: Despite routine echocardiographic surveillance for childhood cancer survivors, the ability to predict cardiomyopathy risk in individual patients is limited. We explored the feasibility and optimal processes for machine learning-enhanced cardiomyopathy prediction in survivors using serial echocardiograms from five centers. METHODS: We designed a series of deep convolutional neural networks (DCNNs) for prediction of cardiomyopathy (shortening fraction ≤ 28% or ejection fraction ≤ 50% on two occasions) for at-risk survivors ≥ 1-year post initial cancer therapy. We built DCNNs with four subsets of echocardiographic data differing in timing relative to case (survivor who developed cardiomyopathy) index diagnosis and two input formats (montages) with differing image selections. We used holdout subsets in a 10-fold cross-validation framework and standard metrics to assess model performance (e.g., F1-score, area under the precision-recall curve [AUPRC]). Performance of the input formats was compared using a combined 5 × 2 cross-validation F-test. RESULTS: The dataset included 542 pairs of montages: 171 montage pairs from 45 cases at time of cardiomyopathy diagnosis or pre-diagnosis and 371 pairs from 70 at-risk survivors who didn't develop cardiomyopathy during follow-up (non-case). The DCNN trained to distinguish between non-case and time of cardiomyopathy diagnosis or pre-diagnosis case montages achieved an AUROC of 0.89 ± 0.02, AUPRC 0.83 ± 0.03, and F1-score: 0.76 ± 0.04. When limited to smaller subsets of case data (e.g., ≥ 1 or 2 years pre-diagnosis), performance worsened. Model input format did not impact performance accuracy across models. CONCLUSIONS: This methodology is a promising first step toward development of a DCNN capable of accurately differentiating pre-diagnosis versus non-case echocardiograms to predict survivors more likely to develop cardiomyopathy.

Syphilis testing, incidence, and reinfection among gay and bisexual men in Australia over a decade spanning HIV PrEP implementation: an analysis of surveillance data from 2012 to 2022.

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.

Social network-based approaches to HIV testing: a systematic review and meta-analysis.

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.

Longitudinal genomic analysis of Neisseria gonorrhoeae transmission dynamics in Australia.

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.

The incubation for urethral gonorrhoea among men who have sex with men with and without oropharyngeal gonorrhoea.

We hypothesized that the incubation for urethral gonorrhoea would be longer for men with oropharyngeal gonorrhoea than those without oropharyngeal gonorrhoea. We conducted a chart review of men who have sex with men with urethral gonorrhoea symptoms at a sexual health clinic between 2019 and 2021. The incubation period was defined as the number of days between men's last sexual contact and onset of symptoms. We used a Mann-Whitney U test to compare differences in the median incubation for urethral gonorrhoea between men with and men without oropharyngeal gonorrhoea. There were 338 men with urethral symptoms (median age = 32 years; IQR: 28-39), and of these, 307 (90.1%) were tested for oropharyngeal gonorrhoea, of whom 124 (40.4%, 95% CI: 34.9-46.1) men had oropharyngeal and urethral gonorrhoea. We analyzed incubation data available for 190 (61.9%) of the 307 men, with 38.9% (74/190) testing positive for oropharyngeal gonorrhoea. The incubation for urethral gonorrhoea did not differ between 74 men (39%) with oropharyngeal gonorrhoea (median = 4 days; IQR: 2-6) and 116 men (61%) without oropharyngeal gonorrhoea (median = 2.5 days; IQR: 1-5) (p = 0.092). Research is needed to investigate gonorrhoea transmission from the oropharynx to the urethra.

Fertility preservation in pediatric central nervous system tumors: A report from the Children's Oncology Group.

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.

Association between saliva use for masturbation and urethral gonorrhoea in men who have sex with men: A cross-sectional study.

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.

Continuity and coordination of care for childhood cancer survivors with multiple chronic conditions: Results from the Childhood Cancer Survivor Study.

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.

Sexual mixing in bisexual activity in male-male partnerships in Melbourne, Australia.

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.

Characterising HIV-1 transmission in Victoria, Australia: a molecular epidemiological study.

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.

A typology of HIV self-testing support systems: a scoping review.

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.

Design and methods of the StepByStep randomized trial of a mobile health and social media physical activity intervention among adolescent and young adult survivors of childhood cancer: A report from the Children's Oncology Group.

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.

Mobile App Promoting Resilience in Stress Management for Adolescents and Young Adults With Cancer: Protocol for a Pilot Randomized Controlled Trial.

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.

Testing effectiveness and implementation of a standardized approach to sexual dysfunction screening among adolescent and young adult-aged survivors of childhood cancer: A type I hybrid, mixed methods trial protocol.

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.

Long-term outcomes among survivors of childhood osteosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).

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.

Changes in HIV post-exposure prophylaxis prescriptions before and after the introduction of HIV pre-exposure prophylaxis at a sexual health clinic in Melbourne, Australia, 2011-2021.

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.

Absenteeism and Health Behavior Trends Associated With Acute Respiratory Illness Before and During the COVID-19 Pandemic in a Community Household Cohort, King County, Washington.

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.

Validation of self-reported human papillomavirus vaccination in young adult men who have sex with men.

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.

The Sexual Health Clinic Role in Vaccine and Treatment Access During the 2022 Mpox Outbreak in King County, Washington.

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.

Prevalence of cefixime-resistant Neisseria gonorrhoeae in Melbourne, Australia, 2021-2022.

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.