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.

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.

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.

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.

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.

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.

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.

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: Effectiveness of sexual dysfunction screening among AYA cancer survivors: a study 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.

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.

Adverse Childhood Experiences, Resilience, and Cardiovascular Disease in Adult Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study.

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.

Chronic Health Conditions and Longitudinal Employment in Survivors of Childhood Cancer.

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.

Trans-Ancestral Genetic Risk Factors for Treatment-Related Type 2 Diabetes Mellitus in Survivors of Childhood Cancer.

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: ORAFR, 20.18; P = .023; OREUR, 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.

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

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.

Modifiable Cardiometabolic Risk Factors in Survivors of Childhood Cancer: JACC: CardioOncology State-of-the-Art Review.

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.

Association of Tecovirimat Therapy With Mpox Symptom Improvement: A Cross-sectional Study-King County, Washington, May-October 2022.

Background: Data on tecovirimat effectiveness for human mpox are limited. We conducted a retrospective cross-sectional interview-based study to identify associations between tecovirimat treatment and the mpox clinical course. Methods: Using public health surveillance data from King County, Washington, we recruited and interviewed persons diagnosed with mpox during May-October 2022. We calculated descriptive statistics on demographics, vaccination status, comorbidities, and symptoms including 3 self-reported dates (symptom onset, first date of symptom improvement, and illness resolution). We used multivariable linear regression, stratified by illness severity, to evaluate the association of tecovirimat treatment with time to symptom improvement and time to illness resolution. We compared individuals who did not receive tecovirimat to participants who started tecovirimat early (≤5 days from symptom onset) and late (>5 days and ≤28 days from symptom onset) in their illness. Results: Of 465 individuals diagnosed with mpox, 115 (25%) participated in this study. Eighty participants (70%) received tecovirimat and 43 (37%) initiated tecovirimat early. Sixty-eight (59%) reported severe symptoms during their illness, including proctitis (n = 38 [33%]), rectal bleeding (n = 27 [24%]), or severe pain (n = 24 [21%]). In the multivariable analysis, early tecovirimat was associated with shorter time to symptom improvement (-5.5 days, P = .04) among participants with severe illness but not among those with nonsevere illness (0.9 day, P = .66). Early tecovirimat was not associated with faster illness resolution, regardless of severity. Conclusions: Our small study suggests that early tecovirimat initiation may hasten subjective symptomatic improvement in people with severe mpox. Larger randomized trials are needed to evaluate this finding.

Remote surveillance and detection of SARS-CoV-2 transmission among household members in King County, Washington.

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.

Utility of apical four-chamber longitudinal strain in the assessment of childhood cancer survivors: A multicenter study.

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.