Ototoxicity refers to the adverse effects of substances on auditory or vestibular functions. This study examines the evidence of ototoxicity's association with exposure to common environmental pollutants, as documented in toxicological profiles by the Agency for Toxic Substances and Disease Registry. Our aim was to evaluate whether the evidence supports modifying the charting of ototoxic effects in the summary tables of these toxicological profiles and providing a guide for scientists to access these data. Health outcomes of interest included hearing loss, vestibular effects, cochlear lesions, tonal alterations, cellular damage, and ototoxicity-related outcomes (neurological, nephrotoxic, hepatic, and developmental effects). We obtained ototoxicity information for 62 substances. Hearing-related effects were reported, along with neurological effects. Overall, 26 profiles reported strong evidence of ototoxicity, including 13 substances previously designated as ototoxic by other health and safety agencies. Commonly studied outcomes included hearing loss, damage to ear anatomy, and auditory dysfunction. Vestibular dysfunction and tinnitus are rarely studied. Our findings highlight the lack of conclusive evidence of ototoxic properties for many substances, especially for pesticides and herbicides. This review supports charting the evidence of ototoxicity separately in toxicological profiles' summary tables. Improving the communication of ototoxicity-related health effects might impact their recognition and prompt further research. A stronger evidence base could support improved prevention efforts in terms of serious health outcomes.

IMPORTANCE: The World Health Organization has called for eliminating cervical cancer as a public health problem. Accurate and up-to-date estimates of population-based cervical cancer incidence are essential for monitoring progress toward elimination and informing local cancer control strategies, but these estimates are lacking for the US-Affiliated Pacific Islands (USAPI). OBJECTIVE: To calculate age-standardized incidence rates for cervical cancer in the 6 USAPI and compare these rates with rates in the US (50 states and the District of Columbia). DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used population-based data from the Pacific Regional Central Cancer Registry for women aged 20 years or older who were diagnosed with invasive cervical cancer from January 1, 2007, to December 31, 2020. The registry comprises data on all cervical cancers from the USAPI, which include 3 US territories (American Samoa, Commonwealth of the Northern Mariana Islands, and Guam) and 3 freely associated states (Federated States of Micronesia [FSM], Republic of the Marshall Islands [RMI], and Republic of Palau). Data were analyzed from July 10, 2023, to November 28, 2023. MAIN OUTCOMES AND MEASURES: The main outcome was age-standardized cervical cancer incidence rates, stratified by age, stage, and histologic code for the USAPI using population estimates from 3 different sources (US Census Bureau International Database, United Nations Population Division, and Pacific Data Hub). Rate ratios were calculated to compare incidence rates between the USAPI and the US. RESULTS: From 2007 to 2020, 409 cases of cervical cancer were diagnosed in the USAPI (median age at diagnosis, 46.0 years [25th-75th percentile, 39.0-55.0 years]), with an age-standardized incidence rate ranging from 21.7 (95% CI, 19.6-23.9) to 22.1 (95% CI, 20.0-24.4) per 100 000 women, depending on the population estimate. Incidence rates were highest in RMI, ranging from 58.1 (95% CI, 48.0-69.7) to 83.4 (95% CI, 68.3-101.0) per 100 000 women, followed by FSM, ranging from 28.7 (95% CI, 23.4-34.9) to 29.8 (95% CI, 24.3-36.3) per 100 000 women. Compared with the US, incidence rates were highest in RMI (rate ratio, 5.7 [95% CI, 4.7-6.8] to 8.2 [95% CI, 6.7-9.9]) and FSM (rate ratio; 2.8; 95% CI, 2.3-3.4). Of all cases in the USAPI, 213 (68.2%) were diagnosed at a late stage. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, cervical cancer remained a major public health issue in some USAPI, with RMI reporting the highest incidence rates. The findings suggest that improvements in human papillomavirus vaccination and cancer screening coverage through efforts tailored to the unique geographic, sociocultural, economic, and health care landscape of the USAPI may reduce the burden of cervical cancer.

INTRODUCTION: Disease intervention specialists (DIS) are critical for delivering partner services programs that provide partner notification, counseling, referral, and other services for HIV, sexually transmitted infections (STIs), and other infections. This systematic review of partner services and other DIS-delivered interventions for HIV and STIs was conducted to summarize the effectiveness of these programs and identify evidence gaps. METHODS: A systematic literature review was conducted with a narrative synthesis. Articles were located using keyword searches in MEDLINE, Web of Science, CINAHL, and ProQuest through December 2022 and analyzed in 2023-2024. Included studies addressed an intervention of partner services or other DIS-delivered services for HIV or STIs; a United States setting; primary data collection; and an external comparison group or pre-post design. RESULTS: 1,915 unique records were screened for eligibility, with 30 studies included. Overall, DIS-delivered interventions improved clinical outcomes among index patients and population outcomes. Many studies focused on program process measures rather than population-level epidemiologic outcomes. All but one studies were scored as having low or medium strength of evidence. DISCUSSION: The evidence could be strengthened by establishing a streamlined set of core metrics, assessing impact using rigorous causal inference methodologies, linking program and clinical data systems, and supplementing impact evaluations with evidence on implementation strategies.

BACKGROUND: Breast cancer is the most common cancer diagnosed among women globally and in the United States (US); however, its incidence in the six US-Affiliated Pacific Islands (USAPI) remains less characterized. METHODS: We analyzed data from a population-based cancer registry using different population estimates to calculate incidence rates for breast cancer among women aged >20 years in the USAPI. Rate ratios and 95 % confidence intervals (CI) were calculated to compare incidence rates between the USAPI and the US (50 states and the District of Columbia). RESULTS: From 2007-2020, 1118 new cases of breast cancer were diagnosed in the USAPI, with 66.3 % (n = 741) of cases reported in Guam. Age-standardized incidence rates ranged from 66.4 to 68.7 per 100,000 women in USAPI and 101.1-110.5 per 100,000 women in Guam. Compared to the US, incidence rates were lower in USAPI, with rate ratios ranging from 0.38 (95 % CI: 0.36, 0.40) to 0.39 (95 % CI: 0.37, 0.42). The proportion of late-stage cancer was significantly higher in the USAPI (48.7 %) than in the US (34.0 %), particularly in the Federated States of Micronesia (78.7 %) and Palau (73.1 %). CONCLUSIONS: Breast cancer incidence rates were lower in the USAPI than in the US; however, late-stage diagnoses were disproportionately higher. Low incidence and late-stage cancers may signal challenges in screening, cancer surveillance, and health care access and resources. Expanding access to timely breast cancer screening, diagnosis, and treatment could reduce the proportion of late-stage cancers and improve survival in the USAPI.

The mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech) provide strong protection against severe COVID-19, including hospitalization, for at least several months after receipt of the second dose (1,2). However, studies examining immune responses and differences in protection against COVID-19-associated hospitalization in real-world settings, including by vaccine product, are limited. To understand how vaccine effectiveness (VE) might change with time, CDC and collaborators assessed the comparative effectiveness of Moderna and Pfizer-BioNTech vaccines in preventing COVID-19-associated hospitalization at two periods (14-119 days and ≥120 days) after receipt of the second vaccine dose among 1,896 U.S. veterans at five Veterans Affairs medical centers (VAMCs) during February 1-September 30, 2021. Among 234 U.S. veterans fully vaccinated with an mRNA COVID-19 vaccine and without evidence of current or prior SARS-CoV-2 infection, serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2 were also compared. Adjusted VE 14-119 days following second Moderna vaccine dose was 89.6% (95% CI = 80.1%-94.5%) and after the second Pfizer-BioNTech dose was 86.0% (95% CI = 77.6%-91.3%); at ≥120 days VE was 86.1% (95% CI = 77.7%-91.3%) for Moderna and 75.1% (95% CI = 64.6%-82.4%) for Pfizer-BioNTech. Antibody levels were significantly higher among Moderna recipients than Pfizer-BioNTech recipients across all age groups and periods since vaccination; however, antibody levels among recipients of both products declined between 14-119 days and ≥120 days. These findings from a cohort of older, hospitalized veterans with high prevalences of underlying conditions suggest the importance of booster doses to help maintain long-term protection against severe COVID-19.(†).

The COVID-19 pandemic has exposed weaknesses in disease surveillance in nearly all countries. Early identification of COVID-19 cases and clusters for rapid containment was hampered by inadequate diagnostic capacity, insufficient contact tracing, fragmented data systems, incomplete data insights for public health responders, and suboptimal governance of all these elements. Once SARS-CoV-2 became widespread, interventions to control community transmission were undermined by weak surveillance of cases and insufficient national capacity to integrate data for timely adjustment of public health measures.1, 2 Although some countries had little or no reliable data, others did not share data consistently with their own populations and with WHO and other multilateral agencies. The emergence of SARS-CoV-2 variants has highlighted inadequate national pathogen genomic sequencing capacities in many countries and led to calls for expanded virus sequencing. However, sequencing without epidemiological and clinical surveillance data is insufficient to show whether new SARS-CoV-2 variants are more transmissible, more lethal, or more capable of evading immunity, including vaccine-induced immunity.3, 4

BACKGROUND AND OBJECTIVE: Community mitigation strategies could help reduce COVID-19 incidence. In a national county-level analysis, we examined the probability of being identified as a county with rapidly increasing COVID-19 incidence (rapid riser identification) during the summer of 2020 by implementation of mitigation policies prior to the summer, overall and by urbanicity. METHODS: We analyzed county-level data on rapid riser identification during June 1-September 30, 2020 and statewide closures and statewide mask mandates starting March 19 (obtained from state government websites). Poisson regression models with robust standard error estimation were used to examine differences in the probability of rapid riser identification by implementation of mitigation policies (P-value<.05); associations were adjusted for county population size. RESULTS: Counties in states that closed for 0-59 days were more likely to become a rapid riser county than those that closed for >59 days, particularly in nonmetropolitan areas. The probability of becoming a rapid riser county was 43% lower among counties that had statewide mask mandates at reopening (adjusted prevalence ratio [aPR] = 0.57; 95% confidence intervals [CI] = 0.51-0.63); when stratified by urbanicity, associations were more pronounced in nonmetropolitan areas. CONCLUSIONS: These results underscore the potential value of community mitigation strategies in limiting the COVID-19 spread, especially in nonmetropolitan areas.

Background: The costs of cancer registration have previously been estimated for registries in the continental United States and many international registries; however, to date, there has been no economic assessment of population-based registries in the US-Affiliated Pacific Islands. This study estimates the costs and factors affecting the operations of US-Affiliated Pacific Island population-based cancer registries. Methods: The web-based International Registry Costing Tool1 was used to collect costs, resources used, cancer cases processed, and other registry characteristics from the Pacific Regional Central Cancer Registry (PRCCR), Federated States of Micronesia National Cancer Registry, and nine satellite jurisdictional registries within the US Pacific Islands. The registries provided data on costs for June 30, 2016-June 29, 2017, and cases processed during 2014. Results: Local host institutions provided a vital source of support for US-Affiliated Pacific Islands registries, covering substantial fixed costs, such as management and overhead. The cost per cancer case processed had an almost tenfold variation across registries, with the average total cost per case of about $1,413. The average cost per inhabitant in the US-Affiliated Pacific Islands was about $1.77 per person. Discussion: The challenges of collecting data from dispersed populations spread across multiple islands of the US-Affiliated Pacific Islands are likely leading factors driving the magnitude of the registries' cost per case. The economic information from this study provides a valuable source of activity-based cost data that can both help guide cancer control initiatives and help registries improve operations and efficiency.

OBJECTIVES: Correlations are made between mainstream cigarette smoke deliveries of individual PAHs over multiple years. Average overall PAH deliveries in mainstream cigarette smoke by study year, mentholation, ring size, and manufacturer are compared. METHODS: Mainstream smoke deliveries were determined by GC/MS for 14 polycyclic aromatic hydrocarbons (PAHs) from selected cigarettes on the US market in 2002, 2004, 2007, and 2011. The mainstream smoke PAH emissions were measured under international standardization organization (ISO) smoking conditions. Pearson product-moment correlation was used to examine the linear relationship among the PAHs over multiple years. RESULTS: A number of the PAH analytes were statistically highly correlated with each other. The overall average for mainstream smoke deliveries of PAHs did not change significantly between study years. Similar levels in average PAH deliveries were seen for mentholated and non-mentholated cigarettes. CONCLUSIONS: The strong correlations between PAH compounds over multiple years show that a limited set of PAHs can predict deliveries of others with confidence over multiple years. A more limited panel of analytes may be considered when designing studies involving PAH measurements in mainstream smoke.

Gasoline direct injection (GDI) engines are increasingly prevalent in the global vehicle fleet. Particulate matter emissions from GDI engines are elevated compared to conventional gasoline engines. The pulmonary effects of these higher particulate emissions are unclear. This study investigated the pulmonary responses induced by GDI engine exhaust using an ex vivo model. The physiochemical properties of GDI engine exhaust were assessed. Precision cut lung slices were prepared using Balb/c mice to evaluate the pulmonary response induced by one-hour exposure to engine-out exhaust from a laboratory GDI engine operated at conditions equivalent to vehicle highway cruise conditions. Lung slices were exposed at an air-liquid interface using an electrostatic aerosol in vitro exposure system. Particulate and gaseous exhaust was fractionated to contrast mRNA production related to polycyclic aromatic hydrocarbon (PAH) metabolism and oxidative stress. Exposure to GDI engine exhaust upregulated genes involved in PAH metabolism, including Cyp1a1 (2.71, SE=0.22), and Cyp1b1 (3.24, SE=0.12) compared to HEPA filtered air (p<0.05). GDI engine exhaust further increased Cyp1b1 expression compared to filtered GDI engine exhaust (i.e., gas fraction only), suggesting this response was associated with the particulate fraction. Exhaust particulate was dominated by high molecular weight PAHs. Hmox1, an oxidative stress marker, exhibited increased expression after exposure to GDI (1.63, SE=0.03) and filtered GDI (1.55, SE=0.04) engine exhaust compared to HEPA filtered air (p<0.05), likely attributable to a combination of the gas and particulate fractions. Exposure to GDI engine exhaust contributes to upregulation of genes related to the metabolism of PAHs and oxidative stress.

Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Effective public health responses to an influenza pandemic require an effective vaccine that can be manufactured and administered to large populations in the shortest possible time. In this study, we evaluated a method for vaccination against avian influenza virus that uses a DNA vaccine for rapid manufacturing and delivered by a microneedle skin patch for simplified administration and increased immunogenicity. We prepared patches containing 700-mcm long microneedles coated with an avian H5 influenza hemagglutinin DNA vaccine from A/Viet Nam/1203/04 influenza virus. The coating DNA dose increased with DNA concentration in the coating solution and the number of dip-coating cycles. Coated DNA was released into the skin tissue by dissolution within minutes. Vaccination of mice using microneedles induced higher levels of antibody responses and hemagglutination inhibition titers, and improved protection against lethal infection with avian influenza as compared to conventional intramuscular delivery of the same dose of the DNA vaccine. Additional analysis showed that the microneedle coating solution containing carboxymethylcellulose and a surfactant may have negatively affected the immunogenicity of the DNA vaccine. Overall, this study shows that DNA vaccine delivery by microneedles can be a promising approach for improved vaccination to mitigate an influenza pandemic.