Estimates of SARS-CoV-2 Hospitalization and Fatality Rates in the Prevaccination Period, United States.

Few precise estimates of hospitalization and fatality rates from COVID-19 exist for naive populations, especially within demographic subgroups. We estimated rates among persons with SARS-CoV-2 infection in the United States during May 1-December 1, 2020, before vaccines became available. Both rates generally increased with age; fatality rates were highest for persons >85 years of age (24%) and lowest for children 1-14 years of age (0.01%). Age-adjusted case hospitalization rates were highest for African American or Black, not Hispanic persons (14%), and case-fatality rates were highest for Asian or Pacific Islander, not Hispanic persons (4.4%). Eighteen percent of hospitalized patients and 44.2% of those admitted to an intensive care unit died. Male patients had higher hospitalization (6.2% vs. 5.2%) and fatality rates (1.9% vs. 1.5%) than female patients. These findings highlight the importance of collecting surveillance data to devise appropriate control measures for persons in underserved racial/ethnic groups and older adults.

Vital Signs: Mammography Use and Association with Social Determinants of Health and Health-Related Social Needs Among Women - United States, 2022.

Introduction: Approximately 40,000 U.S. women die from breast cancer each year. Mammography is recommended to screen for breast cancer and reduce breast cancer mortality. Adverse social determinants of heath (SDOH) and health-related social needs (HRSNs) (e.g., lack of transportation and social isolation) can be barriers to getting mammograms. Methods: Data from the 2022 Behavioral Risk Factor Surveillance System were analyzed to estimate the prevalence of mammography use within the previous 2 years among women aged 40-74 years by jurisdiction, age group, and sociodemographic factors. The association between mammography use and measures of SDOH and HRSNs was assessed for jurisdictions that administered the Social Determinants and Health Equity module. Results: Among women aged 50-74 years, state-level mammography use ranged from 64.0% to 85.5%. Having health insurance and a personal health care provider were associated with having had a mammogram within the previous 2 years. Among women aged 50-74 years, mammography prevalence was 83.2% for those with no adverse SDOH and HRSNs and 65.7% for those with three or more adverse SDOH and HRSNs. Life dissatisfaction, feeling socially isolated, experiencing lost or reduced hours of employment, receiving food stamps, lacking reliable transportation, and reporting cost as a barrier for access to care were all strongly associated with not having had a mammogram within the previous 2 years. Conclusions and Implications for Public Health Practice: Identifying specific adverse SDOH and HRSNs that women experience and coordinating activities among health care providers, social services, community organizations, and public health programs to provide services that help address these needs might increase mammography use and ultimately decrease breast cancer deaths.

Docetaxel Inhibits Epithelial-Mesenchymal Transition in Human Mammary Cells.

Epithelial-mesenchymal transition (EMT) is a reversible and dynamic biological process in which epithelial cells acquire mesenchymal characteristics including enhanced stemness and migratory ability. EMT can facilitate cancer metastasis and is a known driver of cellular resistance to common chemotherapeutic drugs, such as docetaxel. Current chemotherapeutic practices such as docetaxel treatment can promote EMT and increase the chance of tumor recurrence and resistance, calling for new approaches in cancer treatment. Here we show that prolonged docetaxel treatment at a sub-IC50 concentration inhibits EMT in immortalized human mammary epithelial (HMLE) cells. Using immunofluorescence, flow cytometry, and bulk transcriptomic sequencing to assess EMT progression, we analyzed a range of cellular markers of EMT in docetaxel-treated cells and observed an upregulation of epithelial markers and downregulation of mesenchymal markers in the presence of docetaxel. This finding suggests that docetaxel may have clinical applications not only as a cytotoxic drug but also as an inhibitor of EMT-driven metastasis and multidrug resistance depending on the concentration of its use.

Management Practices and Quality of Care: Evidence from the Private Health Care Sector in Tanzania.

We measure the adoption of management practices in over 220 private for-profit and non-profit health facilities in 64 districts across Tanzania and link these data to process quality-of-care metrics, assessed using undercover standardised patients and clinical observations. We find that better managed health facilities are more likely to provide correct treatment in accordance with national treatment guidelines, adhere to a checklist of essential questions and examinations, and comply with infection prevention and control practices. Moving from the 10th to the 90th percentile in the management practice score is associated with a 48% increase in correct treatment. We then leverage a large-scale field experiment of an internationally recognised management support intervention in which health facilities are assessed against comprehensive standards, given an individually tailored quality improvement plan and supported through training and mentoring visits. We find zero to small effects on management scores, suggesting that improving management practices in this setting may be challenging.

The Development and Testing of a Point-of-Sale E-Cigarette Health Communication Campaign.

Adolescents and young adults continue to use e-cigarettes, and communication campaigns are needed to decrease use among these populations. We developed and tested a point-of-sale communication campaign focused on e-cigarette chemical exposure. We developed messages based on formative research and tested them (versus text-only messages) in a nationally-representative online survey among adolescents and young adults (16-25) (Phase 1). Based on survey findings, we selected a message focused on nicotine and brain development for the point-of-sale trial (Phase 2). We then conducted a cluster-randomized trial at six gas stations with convenience stores, randomly assigned to the intervention (messages displayed) or no message control condition. We conducted intercept surveys with repeated cross-sectional samples of 50 participants (ages 16-25) per store, at baseline and a four-week follow-up. Phase 1 included 1,636 participants in the online study. Intervention messages were rated as more attention grabbing than plain text messages (p < .05), though were rated similarly on other outcomes. Exposure to intervention messages resulted in larger changes from pre- to posttest for beliefs about addiction and relative harms versus cigarettes (p < .05). Phase 2 included 586 participants in the point-of-sale study. Real-world campaign exposure was low (31.8%), and no differences were found between conditions. E-cigarette prevention messages focused on nicotine's impact on brain development show promise. However, garnering attention for communication campaigns in saturated point-of-sale environments, often dominated by tobacco advertising, is challenging. Future efforts should utilize additional communication channels to directly target adolescents and young adults.

Intraoperative neural monitoring during head and neck surgery in patients with concern for cervical spine instability.

Cervical and craniocervical instability are associated with catastrophic procedural outcomes. We discuss three individuals who required otolaryngologic surgical intervention: two with symptomatic spinal instability and one in whom spinal stability was unable to be assessed. Two cases were managed with procedural positioning precautions and evoked potential monitoring, and the other with procedural positioning precautions alone. Methods of monitoring and triggers for repositioning are discussed. This series is intended to discuss the approach and potential added value of evoked potential monitoring for risk mitigation in pediatric patients with concern for cervical spine instability.

Acral lentiginous melanoma incidence by sex, race, ethnicity, and stage in the United States, 2010-2019.

INTRODUCTION: Acral lentiginous melanoma (ALM) is a rare type of melanoma associated with delayed diagnosis and poor survival rates. This study examines ALM incidence rates in comparison to all other melanoma types. METHODS: We used data from the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, which together cover 99% of the US population. We calculated age-adjusted rates and rate ratios for ALM and all other malignant melanomas by sex, race and ethnicity, stage, and year of diagnosis (2010-2019). RESULTS: ALM incidence rates were significantly lower among non-Hispanic Black persons (1.8 per 1,000,000); non-Hispanic Asian/Pacific Islander (API) persons (1.7 per 1,000,000); and Hispanic Black, American Indian/Alaska Native (AI/AN), and API persons (1.5 per 1,000,000) compared to non-Hispanic White persons (2.3 per 1,000,000). Rates were significantly higher among Hispanic White persons (2.8 per 1,000,000) compared to non-Hispanic White persons. For all other melanoma types, incidence rates were significantly higher among non-Hispanic White persons compared to persons in each of the other racial and ethnic categories. The percentage of melanomas that were ALM ranged from 0.8% among non-Hispanic White persons to 19.1% among Hispanic Black, AI/AN, and API persons. CONCLUSION: These findings suggest that awareness of the potential for ALM in patients of all races and ethnicities could be balanced with an understanding of the rarity of the disease and the potential for the development of other melanoma types in racial and ethnic minority groups.

Sexual and reproductive healthcare utilisation and affordability for South Sudanese refugees and host populations in Northern Uganda: A mixed methods study.

Given Uganda's increasing refugee population, the health financing burden on refugee and host populations is likely to increase because Uganda's integrated health system caters to both populations. We used sexual, reproductive, and maternal health (SRMH) as a lens to assess the utilisation and user cost of health services in Northern Uganda to identify potential gaps in SRMH services and their financing. We conducted a cross-sectional survey among 2,533 refugee and host women and girls in Arua and Kiryandongo districts. We conducted 35 focus group discussions and 131 in-depth interviews with host and South Sudanese refugees, community members, health workers, NGO and governmental actors. Qualitative data were analysed thematically using a framework approach. Quantitative data were analysed using t-test, chi-square tests, multivariate logistical regression, and a two-part model. We found high levels of access to maternal care services among refugee and host communities in Northern Uganda, but lower levels of met need for family planning (FP). Refugees had higher uptake of delivery care than host communities due to better-resourced refugee facilities, but incurred higher costs for delivery kits and food and less for transport due to facilities being closer. FP uptake was low for both groups due to perceived risks, cultural and religious beliefs, and lack of agency for most women. Host communities lack access to essential maternal healthcare services relative to refugees, especially for delivery care. Greater investment is needed to increase the number of host facilities, improve the quality of SRMH services provided, and further enhance delivery care access among host communities. Ongoing funding of delivery kits across all communities is needed and new financing mechanisms should be developed to support non-medical costs for deliveries, which our study found to be substantial in our study. All populations must be engaged in co-designing improved strategies to meet their FP needs.

G4-DNA formation and chromatin remodelling are interdependent in human cells.

DNA G-quadruplexes (G4s) have been identified as important biological targets for transcriptional, translational, and epigenetic regulation. The stabilisation of G4s with small molecule ligands has emerged as a technique to regulate gene expression and as a potential therapeutic approach for human diseases. Here, we demonstrate that ligand stabilisation of G4s causes altered chromatin accessibility dependent on the targeting specificity of the molecule. In particular, stabilisation of a target G4 using the highly specific GTC365 ligand resulted in differential accessibility of 61 genomic regions, while the broad-targeting G4 ligand, GQC-05, stabilised many G4s and induced a global shift towards increased accessibility of gene promoter regions. Interestingly, while we observed distinct effects of each ligand on RNA expression levels and the induction of DNA double-stranded breaks, both ligands modified DNA damage response pathways. Our work represents the dual possibility of G4-stabilising ligands for specific or global chromatin modulation via unique targeting characteristics.

Counts, incidence rates, and trends of pediatric cancer in the United States, 2003-2019.

BACKGROUND: Cancer is a leading cause of death by disease among children and adolescents in the United States. This study updates cancer incidence rates and trends using the most recent and comprehensive US cancer registry data available. METHODS: We used data from US Cancer Statistics to evaluate counts, age-adjusted incidence rates, and trends among children and adolescents younger than 20 years of age diagnosed with malignant tumors between 2003 and 2019. We calculated the average annual percent change (APC) and APC using joinpoint regression. Rates and trends were stratified by demographic and geographic characteristics and by cancer type. RESULTS: With 248 749 cases reported between 2003 and 2019, the overall cancer incidence rate was 178.3 per 1 million; incidence rates were highest for leukemia (46.6), central nervous system neoplasms (30.8), and lymphoma (27.3). Rates were highest for males, children 0 to 4 years of age, Non-Hispanic White children and adolescents, those in the Northeast census region, the top 25% of counties by economic status, and metropolitan counties with a population of 1 million people or more. Although the overall incidence rate of pediatric cancer increased 0.5% per year on average between 2003 and 2019, the rate increased between 2003 and 2016 (APC = 1.1%), and then decreased between 2016 and 2019 (APC = -2.1%). Between 2003 and 2019, rates of leukemia, lymphoma, hepatic tumors, bone tumors, and thyroid carcinomas increased, while melanoma rates decreased. Rates of central nervous system neoplasms increased until 2017, and then decreased. Rates of other cancer types remained stable. CONCLUSIONS: Incidence of pediatric cancer increased overall, although increases were limited to certain cancer types. These findings may guide future public health and research priorities.

Disparities in incidence and trends of colorectal, lung, female breast, and cervical cancers among non-Hispanic American Indian and Alaska Native people, 1999-2018.

PURPOSE: This study is the first to comprehensively describe incidence rates and trends of screening-amenable cancers (colorectal, lung, female breast, and cervical) among non-Hispanic AI/AN (NH-AI/AN) people. METHODS: Using the United States Cancer Statistics AI/AN Incidence Analytic Database, we, calculated incidence rates for colorectal, lung, female breast, and cervical cancers for NH-AI/AN and non-Hispanic White (NHW) people for the years 2014-2018 combined. We calculated age-adjusted incidence rates (per 100,000), total percent change in incidence rates between 1999 and 2018, and trends over this time-period using Joinpoint analysis. Screening prevalence by region was calculated using Behavioral Risk Factor Surveillance System data. RESULTS: Rates of screening-amenable cancers among NH-AI/AN people varied by geographic region and age at diagnosis. Over half of all lung and colorectal cancers in NH-AI/AN people were diagnosed at later stages. Rates of lung and colorectal cancers decreased significantly between 1999-2018 among NH-AI/AN men, but no significant changes were observed in rates of screening-amenable cancers among NH-AI/AN women. CONCLUSION: This study highlights disparities in screening-amenable cancers between NH-AI/AN and NHW people. Culturally informed, community-based interventions that increase access to preventive health services could reduce cancer disparities among AI/AN people.

Extrahepatic transplantation of 3D cultured stem cell-derived islet organoids on microporous scaffolds.

Stem cell differentiation methods have been developed to produce cells capable of insulin secretion which are showing promise in clinical trials for treatment of type-1 diabetes. Nevertheless, opportunities remain to improve cell maturation and function. Three-dimensional (3D) culture has demonstrated improved differentiation and metabolic function in organoid systems, with biomaterial scaffolds employed to direct cell assembly and facilitate cell-cell contacts. Herein, we investigate 3D culture of human stem cell-derived islet organoids, with 3D culture initiated at the pancreatic progenitor, endocrine progenitor, or immature ß-cell stage. Clusters formed by reaggregation of immature ß-cells could be readily seeded into the microporous poly(lactide-co-glycolide) scaffold, with control over cell number. Culture of islet organoids on scaffolds at the early to mid-stage beta cell progenitors had improved in vitro glucose stimulated insulin secretion relative to organoids formed at the pancreatic progenitor stage. Reaggregated islet organoids were transplanted into the peritoneal fat of streptozotocin-induced diabetic mice, which resulted in reduced blood glucose levels and the presence of systemic human C-peptide. In conclusion, 3D cell culture supports development of islet organoids as indicated by insulin secretion in vitro and supports transplantation to extrahepatic sites that leads to a reduction of hyperglycemia in vivo.

Use of Behavior Change Techniques and Quality of Commercially Available Inflammatory Bowel Disease Apps.

BACKGROUND: Inclusion of evidence-based behavior change techniques (e.g., self-monitoring) in mobile health apps has the potential to promote adherence to inflammatory bowel disease treatment. While inflammatory bowel disease management apps exist, the extent to which they incorporate behavior change techniques remains unknown. AIMS: The present study systematically evaluated the content and quality of free, commercially available inflammatory bowel disease management apps. METHODS: Apps were identified using a systematic search of the Apple App and Google Play stores. Apps were evaluated using Abraham and Michie's taxonomy of 26 behavior change techniques. A literature search was conducted to identify behavior change techniques specific and relevant for people with inflammatory bowel disease. App quality was assessed using the Mobile App Rating Scale with scores ranging from 1 (Inadequate) to 5 (Excellent). RESULTS: A total of 51 inflammatory bowel disease management apps were evaluated. Apps included 0-16 behavior change techniques (Mean = 4.55) and 0-10 inflammatory bowel disease management behavior change techniques (Mean = 3.43). App quality ranged from 2.03 to 4.62 (Mean = 3.39) out of 5.00. Two apps, My IBD Care: Crohn's & Colitis and MyGiHealth GI Symptom Tracker, included the highest number of overall and inflammatory bowel disease management behavior change techniques along with high-quality scores. Bezzy IBD was the only app with a high number of overall and inflammatory bowel disease management behavior change techniques with a primary focus on social support/change. CONCLUSION: Most inflammatory bowel disease management apps reviewed included evidence-based inflammatory bowel disease management behavior change techniques.

Does increased provider effort improve quality of care? Evidence from a standardised patient study on correct and unnecessary treatment.

BACKGROUND: Poor quality of care, including overprovision (unnecessary care) is a global health concern. Greater provider effort has been shown to increase the likelihood of correct treatment, but its relationship with overprovision is less clear. Providers who make more effort may give more treatment overall, both correct and unnecessary, or may have lower rates of overprovision; we test which is true in the Tanzanian private health sector. METHODS: Standardised patients visited 227 private-for-profit and faith-based facilities in Tanzania, presenting with symptoms of asthma and TB. They recorded history questions asked and physical examinations carried out by the provider, as well as laboratory tests ordered, treatments prescribed, and fees paid. A measure of provider effort was constructed on the basis of a checklist of recommended history taking questions and physical exams. RESULTS: 15% of SPs received the correct care for their condition and 74% received unnecessary care. Increased provider effort was associated with increased likelihood of correct care, and decreased likelihood of giving unnecessary care. Providers who made more effort charged higher fees, through the mechanism of higher consultation fees, rather than increased fees for lab tests and drugs. CONCLUSION: Providers who made more effort were more likely to treat patients correctly. A novel finding of this study is that they were also less likely to provide unnecessary care, suggesting it is not simply a case of some providers doing "more of everything", but that those who do more in the consultation give more targeted care.

Comparison of computerized provider order entry specific transfusion indications versus the use of "Other".

BACKGROUND: Computerized physician order entry (CPOE) systems are one way to reinforce evidence-based transfusion indications for blood products. The new CPOE system that was implemented at our institution allowed healthcare providers to select "Other" as an indication and provide reasons for transfusion outside of accepted guidelines. STUDY DESIGN AND METHODS: Transfusion order records for packed red blood cells (RBCs), platelets, and fresh frozen plasma (FFP) from high product-ordering areas of Long Island Jewish Medical Center and Cohen's Children's Medical Center from April 2021, when the new CPOE system was implemented, to November 2021 were reviewed. The percentage of "Other" orders was determined and the reason for each "Other" order was reviewed to identify possible areas for education or valid indications not included in the institutionally recognized indications. RESULTS: 9.7% of RBC orders, 1.9% of platelet orders, and 18.2% of FFP orders were placed with "Other" as the indication for transfusion (χ2 2  = 88.5; p < .001). Reasons for "Other" orders were varied, but notable reasons included indications already institutionally accepted such as, bleeding (15.7% of pediatric "Other" RBC orders), hold for OR (14.3% of pediatric and 15.8% of adult "Other" RBC orders), and novel reasons such as FFP for ACE-inhibitor associated angioedema (84.6% of adult "Other" FFP orders). DISCUSSION: The findings from our study provide examples of potential difficulties hospitals may encounter when they implement a new computerized physician order entry system. Provider education may play an important role to reduce the number of "Other" orders placed for already recognized indications.

Point-of-Sale Health Communication Campaigns for Cigarillos and Waterpipe Tobacco: Effects and Lessons Learned from Two Cluster Randomized Trials.

Many adolescents and young adults hold erroneous beliefs that cigarillos and waterpipe tobacco (WT) are safer than cigarettes, contributing to use. Communication campaigns can correct misperceptions and increase risk beliefs. We tested point-of-sale (POS) communication campaigns focused on chemical exposure for cigarillos and WT. We conducted two cluster randomized trials at 20 gas stations with convenience stores (10 stores for cigarillos, 10 for WT) in North Carolina between June and November 2017. Within each trial, stores were randomly assigned to either the intervention (campaign messages displayed) or a no message control condition. We conducted intercept surveys with repeated cross-sectional samples of 50 adolescents and young adults (ages 16-25) per store, at baseline and follow-up. There were 978 participants (mean age = 20.9 years) in the cigarillo trial, and 998 participants (mean age = 21.0 years) in the WT trial. Rates of campaign exposure were low (26% for cigarillos; 24.3% for WT). The cigarillo campaign increased knowledge that ammonia is in cigarillo smoke (p < .01). There were also significant increases in knowledge about ammonia and cyanide in cigarillo smoke and arsenic in WT smoke (p < .05) in the sub-sample who reported exposure to the campaign. No differences were found in outcome expectancies, product attitudes, worry about chemical exposure, or behavioral intentions in either campaign. Garnering attention for communication campaigns in saturated POS environments, often dominated by tobacco advertising, is challenging. Our study demonstrates the feasibility of anti-tobacco campaigns at the POS and points to several lessons learned for future POS campaigns.

Responses to pictorial versus text-only cigarillo warnings among a nationally representative sample of US young adults.

BACKGROUND: The US Food and Drug Administration requires six text-only warnings for cigar products, including cigarillos. Research has demonstrated the superiority of pictorial over text-only cigarette warnings, yet the relative effectiveness of pictorial warnings for cigarillos has not been examined. We examined the impact of pictorial cigarillo warnings compared with text-only warnings. METHODS: Data were collected from a nationally representative sample of US young adult (18-29) cigarillo users and susceptible non-users. Participants were randomised to one of three experimental conditions: text-only or one of two pictorial conditions (combined for analyses). For each warning, we assessed negative emotional reactions, cognitive elaboration (ie, thinking about cigarillo risks) and perceived message effectiveness (PME). RESULTS: Participants (N=661) were 46.5% female, 64.7% white and 21.9% Hispanic; 34.1% reported past 30-day cigarillo use; 41.4% were lifetime users (excluding past 30-day use); and 24.4% were susceptible non-users. Pictorial warnings elicited more negative emotional reactions and higher PME than text-only warnings (p values<0.01), with interactions showing the largest effects for past 30-day users (emotional reactions: d=0.99, PME: d=0.63). For cognitive elaboration, there was no main effect of warning type, but an interaction revealed effects for past 30-day users (p<0.05, d=0.46). CONCLUSIONS: Pictorial cigarillo warnings elicited greater negative emotional reactions and PME compared with text-only warnings. These effects and the effects on cognitive elaboration were strongest for past 30-day users. Our findings extend research on cigarette warnings to cigarillos, demonstrating that pictorial warnings are superior to text-only warnings for cigarillos in eliciting beneficial responses.

The histone acetyltransferase KAT6A is recruited to unmethylated CpG islands via a DNA binding winged helix domain.

The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrate that a winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A with unmethylated CpG islands (CGIs) genome-wide. Mutation of the essential amino acids for DNA binding completely abrogates the enrichment of KAT6A at CGIs. In contrast, deletion of a second WH domain or the histone tail binding PHD fingers only subtly influences the binding of KAT6A to CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases.