BACKGROUND: With accumulating evidence of single-dose human papillomavirus (HPV) vaccine efficacy in young women, we conducted a community vaccine effectiveness study comparing HPV single-dose and 2-dose regimens (0 and 6 months) of a bivalent HPV vaccine among grade 8 schoolgirls (aged 13-14 years) in Thailand. METHODS: In 2018, eligible grade 8 schoolgirls in Udon Thani (single dose) and Buri Ram (2 doses) provinces were offered HPV vaccine per assigned dose regimen. Concurrently, a cross-sectional survey for measuring baseline HPV prevalence was conducted in grade 10 (n = 2600) and grade 12 unvaccinated schoolgirls (n = 2000) in each province. HPV infection was assessed in first-void urine samples, tested by DNA polymerase chain reaction on the cobas 4800 system (Roche Molecular Diagnostics, Pleasanton, CA). All samples positive on the cobas system and an equal number of negative samples were also tested by Anyplex II HPV28 Detection (Seegene, Seoul, South Korea). The surveys were repeated in 2020 and 2022, when vaccinated grade 8 schoolgirls reached grade 10, and then subsequently grade 12, respectively. Vaccine effectiveness was estimated by comparing the weighted prevalence of HPV-16 or HPV-18 between grade-matched unvaccinated schoolgirls on the baseline survey (2018) and vaccinated schoolgirls in the year-2 (2020) and year-4 (2022) surveys. Adjustment methods were used in the analysis to account for potential differences in sexual behavior due to the noncontemporaneous comparison. RESULTS: The prevalence of HPV-16 and HPV-18 on the baseline survey among unvaccinated grade 10/grade 12 schoolgirls was 2.90% (95% confidence interval [CI] = 2.54% to 3.31%)/3.98% (95% CI = 3.52% to 4.49%) for Udon Thani and 3.87% (95% CI = 3.46% to 4.34%)/6.13% (95% CI = 5.56% to 6.75%) for Buri Ram. On the year-2 survey, the prevalence among vaccinated grade 10 schoolgirls was 0.57% (95% CI = 0.42% to 0.77%) for Udon Thani and 0.31% (95% CI = 0.21% to 0.47%) for Buri Ram. The 2-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 80.4% (95% CI = 73.9% to 86.9%), and for the 2-dose regimen at 91.9% (95% CI = 88.5% to 95.4%). On the year-4 survey, the prevalence among vaccinated grade 12 schoolgirls was 0.37% (95% CI = 0.25% to 0.56%) for Udon Thani and 0.28% (95% CI = 0.18% to 0.45%) for Buri Ram. Four-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 90.6% (95% CI = 86.6% to 94.6%) and for the 2-dose regimen was estimated at 95.4% (95% CI = 93.2% to 97.6%). All adjustment methods minimally affected vaccine effectiveness for the single-dose and 2-dose regimens. At 4 years after vaccination, the difference in crude vaccine effectiveness between the single-dose and 2-dose regimens was ‒4.79% (95% CI = ‒9.32% to ‒0.25%), meeting the study's noninferiority criteria. CONCLUSIONS: Our study demonstrated that both single-dose and 2-dose HPV vaccination significantly decreased HPV-16/18 point prevalence 2 years and 4 years after vaccination. Crude vaccine effectiveness at 4 years after vaccination was greater than 90% for both the single-dose and 2-dose regimens; the single-dose regimen was not inferior to the 2-dose regimen. These data show that a single dose of HPV vaccine provides high levels of protection when administered to schoolgirls younger than 15 years of age.

INTRODUCTION: An error grid compares measured versus reference glucose concentrations to assign clinical risk values to observed errors. Widely used error grids for blood glucose monitors (BGMs) have limited value because they do not also reflect clinical accuracy of continuous glucose monitors (CGMs). METHODS: Diabetes Technology Society (DTS) convened 89 international experts in glucose monitoring to (1) smooth the borders of the Surveillance Error Grid (SEG) zones and create a user-friendly tool-the DTS Error Grid; (2) define five risk zones of clinical point accuracy (A-E) to be identical for BGMs and CGMs; (3) determine a relationship between DTS Error Grid percent in Zone A and mean absolute relative difference (MARD) from analyzing 22 BGM and nine CGM accuracy studies; and (4) create trend risk categories (1-5) for CGM trend accuracy. RESULTS: The DTS Error Grid for point accuracy contains five risk zones (A-E) with straight-line borders that can be applied to both BGM and CGM accuracy data. In a data set combining point accuracy data from 18 BGMs, 2.6% of total data pairs equally moved from Zones A to B and vice versa (SEG compared with DTS Error Grid). For every 1% increase in percent data in Zone A, the MARD decreased by approximately 0.33%. We also created a DTS Trend Accuracy Matrix with five trend risk categories (1-5) for CGM-reported trend indicators compared with reference trends calculated from reference glucose. CONCLUSION: The DTS Error Grid combines contemporary clinician input regarding clinical point accuracy for BGMs and CGMs. The DTS Trend Accuracy Matrix assesses accuracy of CGM trend indicators.

BACKGROUND: The Women's Health Needs Study (WHNS) collected information on the health characteristics, needs, and experiences, including female genital mutilation (FGM) experiences, attitudes, and beliefs, of women aged 18 to 49 years who were born, or whose mothers were born, in a country where FGM is prevalent living in the US. The purpose of this paper is to describe the WHNS design, methods, strengths and limitations, as well as select demographic and health-related characteristics of participants. METHODS: We conducted a cross-sectional survey from November 2020 -June 2021 in four US metropolitan areas, using a hybrid venue-based sampling (VBS) and respondent-driven sampling (RDS) approach to identify women for recruitment. RESULTS: Of 1,132 participants, 395 were recruited via VBS and 737 RDS. Most were born, or their mothers were born, in either a West African country (Burkina Faso, Guinea, Mali, Mauritania, Sierra Leone, The Gambia) (39.0%) or Ethiopia (30.7%). More than a third were aged 30-39 years (37.5%) with a majority who immigrated at ages ≥13 years (86.6%) and had lived in the United States for ≥5 years (68.9%). Medicaid was the top health insurer (52.5%), followed by private health insurance (30.5%); 17% of participants had no insurance. Nearly half of women reported 1-2 healthcare visits within the past 12 months (47.7%). One in seven did not get needed health care due to cost (14.8%). Over half have ever used contraception (52.1%) to delay or avoid pregnancy and 76.9% had their last pelvic and/or Papanicolaou (pap) exam within the past 3 years. More than half experienced FGM (55.0%). Nearly all women believed that FGM should be stopped (92.0%). CONCLUSION: The VBS/RDS approach enabled recruitment of a diverse study population. WHNS advances research related to the health characteristics, needs, and experiences of women living in the US from countries where FGM is prevalent.

The global shipping network (GSN) has been suggested as a pathway for the establishment and reintroduction of Aedes aegypti and Aedes albopictus primarily via the tire trade. We used historical maritime movement data in combination with an agent-based model to understand invasion risk in the United States Gulf Coast and how the risk of these invasions could be reduced. We found a strong correlation between the total number of cargo ship arrivals at each port and likelihood of arrival by both Ae. aegypti and Ae. albopictus. Additionally, in 2012, 99.2% of the arrivals into target ports had most recently visited ports likely occupied by both Ae. aegypti and Ae. albopictus, increasing risk of Aedes invasion. Our model results indicated that detection and removal of mosquitoes from containers when they are unloaded effectively reduced the probability of mosquito populations establishment even when the connectivity of ports increased. To reduce the risk of invasion and reintroduction of Ae. aegypti and Ae. albopictus, surveillance and control efforts should be employed when containers leave high risk locations and when they arrive in ports at high risk of establishment.

OBJECTIVE: To examine the relationship between stroke care infrastructure and stroke quality-of-care outcomes at 29 spoke hospitals participating in the <name concealed for blinding purposes> hub-and-spoke telestroke network. MATERIALS AND METHODS: Encounter-level data from <name concealed for blinding purposes> telestroke patient registry were filtered to include encounters during 2015-2022 for patients aged 18 and above with a clinical diagnosis of acute ischemic stroke, and who received intravenous tissue plasminogen activator. Unadjusted and adjusted generalized estimating equations assessed associations between time-related stroke quality-of-care metrics captured during the encounter and the existence of the two components of stroke care infrastructure-stroke coordinators and stroke center certifications-across all hospitals and within hospital subgroups defined by size and rurality. RESULTS: Telestroke encounters at spoke hospitals with stroke coordinators and stroke center certifications were associated with shorter door-to-needle (DTN) times (60.9 min for hospitals with both components and 57.3 min for hospitals with one, vs. 81.2 min for hospitals with neither component, p <.001). Similar patterns were observed for the percentage of encounters with DTN time of ≤60 min (63.8% and 68.9% vs. 32.0%, p <.001) and ≤45 min (34.0% and 38.4% vs. 8.42%, p <.001). Associations were similar for other metrics (e.g., door-to-registration time), and were stronger for smaller (vs. larger) hospitals and rural (vs. urban) hospitals. CONCLUSIONS: Stroke coordinators or stroke center certifications may be important for stroke quality of care, especially at spoke hospitals with limited resources or in rural areas.

BACKGROUND: Most studies on bystander cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) have focused on in-hospital or short-term survival. OBJECTIVES: The purpose of this study was to examine the association between bystander CPR and long-term survival outcomes for OHCA. METHODS: Within the Cardiac Arrest Registry to Enhance Survival, we identified 152,653 patients with OHCA ≥65 years of age or older. Using multivariable hierarchical logistic regression, we first examined the association between bystander CPR and in-hospital survival. Then, among those surviving to discharge and linked to Medicare files, we evaluated the association between bystander CPR and long-term mortality over 5 years using multivariable Cox regression. RESULTS: Overall, 58,464 (38.3%) received bystander CPR. Patients receiving bystander CPR were more likely to have an OHCA that was witnessed, in a public location, and with an initial shockable rhythm. Bystander CPR was associated with a 24% higher likelihood of surviving to hospital discharge (10.2% vs 5.5%; adjusted relative risk: 1.24 [95% CI: 1.19-1.29]; P < 0.001), and this survival benefit was similar (interaction P = 0.24) for those who were 65 to 74, 75 to 84, and ≥85 years of age. Among patients surviving to hospital discharge (median follow-up of 31 months), bystander CPR was additionally associated with lower long-term mortality vs those without bystander CPR (adjusted hazard ratio: 0.78 [95% CI: 0.73-0.84]; P < 0.001), and this benefit was also consistent across age groups (interaction P = 0.13). CONCLUSIONS: In older adults with OHCA, bystander CPR was associated with higher rates of in-hospital survival. This survival benefit was not attenuated by competing mortality risks but increased in magnitude after hospital discharge.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 receptors differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink (Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 receptors. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 receptor is bound to the receptor-binding domain (RBD) of the S glycoprotein in a "down" position, approximately 34° lower than previously reported "up" RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry.

Early detection of pulmonary responses to silica aerosol exposure, such as lung inflammation as well as early identification of silicosis initiation, is of great importance in disease prevention of workers. In this study, to early screen the health condition of the workers who are exposed to respirable silica dusts, an immunoassay lab on a chip (LOC) was designed, developed and fully characterized for analyzing Clara cell protein 16 (CC16) in serum which has been considered as one of the potential biomarkers of lung inflammation or lung damage due to the respirable silica dusts. Sandwich immunoassay of CC16 was performed on the LOC developed with a custom-designed portable analyzer using artificial serums spiked with CC16 protein first and then human serums obtained from the coal mine workers exposed to the respirable silica-containing dusts. The dynamic range of CC16 assay performed on the LOC was in a range of 0.625–20 ng/mL, and the achieved limit of detection (LOD) was around 0.35 ng/mL. The assay results of CC16 achieved from both the developed LOC and the conventional 96 well plate showed a reasonable corelation. The correlation between the conventional reader and the developed portable analyzer was found to be reasonable, resulting in R 2 ~ 0.93. This study shows that the LOC developed for the early detection of CC16 can be potentially applied for the development of a field-deployable point-of-care testing (POCT) for the early monitoring of the field workers who are exposed to silica aerosol. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

The global shipping network (GSN) has been suggested as a pathway for the establishment and reintroduction of Aedes aegypti and Aedes albopictus primarily via the tire trade. We used historical maritime movement data in combination with an agent-based model to understand invasion risk in the United States Gulf Coast and how the risk of these invasions could be reduced. We found a strong correlation between the total number of cargo ship arrivals at each port and likelihood of arrival by both Ae. aegypti and Ae. albopictus. Additionally, in 2012, 99.2% of the arrivals into target ports had most recently visited ports occupied by both Ae. aegypti and Ae. albopictus, increasing risk of Aedes invasion. Model results indicated that detection and removal of mosquitoes from containers when they are unloaded at a port may be more effective in reducing the establishment of mosquito populations compared to eradication efforts that occur while onboard the vessel, suggesting detection efforts should be focused on unloaded containers. To reduce the risk of invasion and reintroduction of Ae. aegypti and Ae. albopictus, surveillance and control efforts should be employed when containers leave high risk locations and when they arrive in ports at high risk of establishment. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Anopheles stephensi is an efficient malaria vector commonly found in South Asia and the Arabian Peninsula, but in recent years it has established as an invasive species in the Horn of Africa (HoA). In this region, An. stephensi was first detected in a livestock quarantine station near a major seaport in Djibouti in 2012, in Ethiopia in 2016, in Sudan in 2018 and Somalia in 2019. Anopheles stephensi often uses artificial containers as larval habitats, which may facilitate introduction through maritime trade as has been seen with other invasive container breeding mosquitoes. If An. stephensi is being introduced through maritime traffic, prioritization exercises are needed to identify locations at greatest risk of An. stephensi introduction for early detection and rapid response, limiting further invasion opportunities. Here, we use UNCTAD maritime trade data to 1) identify coastal African countries which were most highly connected to select An. stephensi endemic countries in 2011, prior to initial detection in Africa, 2) develop a ranked prioritization list of countries based on likelihood of An. stephensi introduction for 2016 and 2020 based on maritime trade alone and maritime trade and habitat suitability, and 3) use network analysis to describe intracontinental maritime trade and eigenvector centrality to determine likely paths of further introduction on the continent if An. stephensi is detected in a new location. Our results show that in 2011, Sudan and Djibouti were ranked as the top two countries with likelihood of An. stephensi introduction based on maritime trade alone, and these were indeed the first two coastal countries in the HoA where An. stephensi was detected. Trade data from 2020 with Djibouti and Sudan included as source populations identify Egypt, Kenya, Mauritius, Tanzania, and Morocco as the top five countries with likelihood of An. stephensi introduction. When factoring in habitat suitability, Egypt, Kenya, Tanzania, Morocco, and Libya are ranked highest. Network analysis revealed that the countries with the highest eigenvector centrality scores, and therefore highest degrees of connectivity with other coastal African nations were South Africa (0.175), Mauritius (0.159), Ghana (0.159), Togo (0.157), and Morocco (0.044) and therefore detection of An. stephensi in any one of these locations has a higher potential to cascade further across the continent via maritime trade than those with lower eigenvector centrality scores. Taken together, these data could serve as tools to prioritize efforts for An. stephensi surveillance and control in Africa. Surveillance in seaports of countries at greatest risk of introduction may serve as an early warning system for the detection of An. stephensi, providing opportunities to limit further introduction and expansion of this invasive malaria vector in Africa. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Team-based care approaches are effective at improving hypertension control and have been used in clinical practice to improve hypertension outcomes. This study implemented and evaluated the Hypertension Management Program (HMP), which was originally developed in a high-resource health setting, in a health system with fewer resources and a patient population disproportionately affected by hypertension. Our objectives were to describe how a health system could adapt HMP to meet their needs and calculate total program costs. HMP uses a team-based, patient-centered approach involving clinical pharmacists who contribute to managing patients who have hypertension and ultimately preventing premature death due to uncontrolled hypertension. HMP has 10 components (e.g., EHR patient registries and outreach lists, no copayment walk-in blood pressure checks). Our project involved implementing the key components of HMP in a federally qualified health center (FQHC) in South Carolina. Adaptations from the key components of HMP were made to fit the participants' settings. A mixed-methods evaluation assessed implementation processes, program costs, and implementation facilitators and barriers. From September 2018 to December 2019, clinical pharmacists conducted 758 hypertension management visits (HMVs) with 316 patients with hypertension. Total program costs for HMP were $325,532 overall and $16,277 per month. Monthly cost per patient was $3.62. The high engagement among clinical pharmacists, along with provider engagements, followed up by the subsequent referral of patients to HMP, facilitated the implementation process. Staff members observed improvements in hypertension control, which increased participation buy-in. Barriers included staff turnover, the perception among some providers that HMP took too much time, as well as perception of HMP as a pharmacy-specific initiative. A team-based, patient-centered approach to hypertension management can be adapted for FQHCs or similar settings that serve patient populations disproportionately affected by hypertension.

The objective of this study was to examine effectiveness of a Hypertension Management Program (HMP) in a Federally Qualified Health Center (FQHC). From September 2018 through December 2019, we implemented HMP in seven clinics of an FQHC in rural South Carolina. A pre/post evaluation design estimated the association of HMP with hypertension control rates and systolic blood pressure using electronic health record data among 3,941 patients. A chi-square test estimated change in mean control rates in pre- and intervention periods. A multilevel multivariable logistic regression model estimated the incremental impact of HMP on odds of hypertension control. Results showed that 53.4% of patients had controlled hypertension pre-intervention (September 2016-September 2018); 57.3% had controlled hypertension at the end of the observed implementation period (September 2018-December 2019) (p < 0.01). Statistically significant increases in hypertension control rates were observed in six of seven clinics (p < 0.05). Odds of controlled hypertension were 1.21 times higher during the intervention period compared to pre-intervention (p < 0.0001). Findings can inform the replication of HMP in FQHCs and similar health care settings, which play a pivotal role in caring for patients with health and socioeconomic disparities.

BACKGROUND: The use of telehealth for the management and treatment of hypertension and cardiovascular disease (CVD) has increased across the United States (U.S.), especially during the COVID-19 pandemic. Telehealth has the potential to reduce barriers to accessing health care and improve clinical outcomes. However, implementation, outcomes, and health equity implications related to these strategies are not well understood. The purpose of this review was to identify how telehealth is being used by U.S. health care professionals and health systems to manage hypertension and CVD and to describe the impact these telehealth strategies have on hypertension and CVD outcomes, with a special focus on social determinants of health and health disparities. METHODS: This study comprised a narrative review of the literature and meta-analyses. The meta-analyses included articles with intervention and control groups to examine the impact of telehealth interventions on changes to select patient outcomes, including systolic and diastolic blood pressure. A total of 38 U.S.-based interventions were included in the narrative review, with 14 yielding data eligible for the meta-analyses. RESULTS: The telehealth interventions reviewed were used to treat patients with hypertension, heart failure, and stroke, with most interventions employing a team-based care approach. These interventions utilized the expertise of physicians, nurses, pharmacists, and other health care professionals to collaborate on patient decisions and provide direct care. Among the 38 interventions reviewed, 26 interventions utilized remote patient monitoring (RPM) devices mostly for blood pressure monitoring. Half the interventions used a combination of strategies (e.g., videoconferencing and RPM). Patients using telehealth saw significant improvements in clinical outcomes such as blood pressure control, which were comparable to patients receiving in-person care. In contrast, the outcomes related to hospitalizations were mixed. There were also significant decreases in all-cause mortality when compared to usual care. No study explicitly focused on addressing social determinants of health or health disparities through telehealth for hypertension or CVD. CONCLUSIONS: Telehealth appears to be comparable to traditional in-person care for managing blood pressure and CVD and may be seen as a complement to existing care options for some patients. Telehealth can also support team-based care delivery and may benefit patients and health care professionals by increasing opportunities for communication, engagement, and monitoring outside a clinical setting.

OBJECTIVE: The aim of this study was to determine the prevalence of high-risk (HR) and vaccine-type human papillomavirus (HPV) infection among Thai schoolgirls who were not included in the national HPV immunization program. METHODS: Cross-sectional surveys were conducted among grade 10 (15-16 years old) and grade 12 (17-18 years old) schoolgirls in two provinces of Thailand. Urine samples were collected using the Colli-Pee(Ⓡ) device from November 2018 to February 2019. The samples were initially tested using Cobas(Ⓡ) 4800. Subsequently, all Cobas-positive samples and 1:1 matched Cobas-negative samples were tested by Anyplex(Ⓡ) assay. Prevalences of any HPV, any HR HPV, vaccine-type HPV, and individual HR HPV types were estimated by school grade. RESULTS: Prevalences of any HPV and any HR HPV were 11.6% and 8.6% for grade 10, and 18.5% and 12.4% for grade 12 schoolgirls, respectively. Prevalences of bivalent vaccine-type HPV infection in grades 10 and 12 were 3.4% and 4.5%, respectively. Prevalences of quadrivalent and nonavalent vaccine-type HPV infections were 4.0%/6.6% and 6.4%/10.4% in grades 10 and 12, respectively. HPV16 was the most common type detected, followed by HPV58, 51, and 52. Circulating HR HPV types were similar between the school grades. CONCLUSION: A substantial burden of HR HPV infections was found among unvaccinated high school girls in Thailand.

Anopheles stephensi, an invasive malaria vector native to South Asia and the Arabian Peninsula, was detected in Djibouti's seaport, followed by Ethiopia, Sudan, Somalia, and Nigeria. If An. stephensi introduction is facilitated through seatrade, similar to other invasive mosquitoes, the identification of at-risk countries are needed to increase surveillance and response efforts. Bilateral maritime trade data is used to (1) identify coastal African countries which were highly connected to select An. stephensi endemic countries, (2) develop a prioritization list of countries based on the likelihood of An. stephensi introduction through maritime trade index (LASIMTI), and (3) use network analysis of intracontinental maritime trade to determine likely introduction pathways. Sudan and Djibouti were ranked as the top two countries with LASIMTI in 2011, which were the first two coastal African countries where An. stephensi was detected. With Djibouti and Sudan included as source populations, 2020 data identify Egypt, Kenya, Mauritius, Tanzania, and Morocco as the top countries with LASIMTI. Network analysis highlight South Africa, Mauritius, Ghana, and Togo. These tools can prioritize efforts for An. stephensi surveillance and control in Africa. Surveillance in seaports of identified countries may limit further expansion of An. stephensi by serving as an early warning system.

BACKGROUND: Most studies on out-of-hospital cardiac arrest have primarily focused on in-hospital or short-term survival. Little is known about long-term outcomes and resource use among survivors of out-of-hospital cardiac arrest. METHODS: In this observationsl study, we describe overall long-term outcomes for patients from the national Cardiac Arrest Registry to Enhance Survival linked to Medicare files to create the Cardiac Arrest Registry to Enhance Survival: Mortality, Events, and Costs for Cardiac Arrest survivors dataset. Cardiac Arrest Registry to Enhance Survival data between 2013 and 2019 were linked to Medicare data using probabilistic matching algorithms. Overall long-term mortality, readmissions, and index hospitalization costs are reported for the overall cohort. RESULTS: Among 56 425 patients who were 65 years of age or older in Cardiac Arrest Registry to Enhance Survival who survived to hospital admission, 26 875 (47.6%) were successfully linked to Medicare files. Mean (+SD) cost of the index hospitalization was $23 262+$24 199 and the median cost was $14 636 (interquartile range, $9930-$30 033). Overall, 8676 (32.3%) survived to hospital discharge with 38.0% discharged home, 11.8% to hospice care, and the remaining 50.2% to other inpatient, skilled nursing care, or rehabilitation facilities. Mortality after discharge was initially high (27.0% at 3 months) and then increased gradually, with 1- and 3-year mortality of 37.1% and 50.1%, respectively. During the first year, 40.1% were readmitted at least once, with 19.7% readmitted on > 1 occasion. CONCLUSIONS: The Cardiac Arrest Registry to Enhance Survival: Mortality, Events, and Costs for Cardiac Arrest survivors registry includes rich data on postdischarge outcomes and resource utilization. Use of this dataset will enable future investigations on the long-term effectiveness, costs, and cost-effectiveness of various interventions for out-of-hospital cardiac arrest in elderly patients.

Human papillomavirus (HPV) is a common infection principally spread through sexual activity. Most HPV infections are asymptomatic and resolve spontaneously. However, persistent infection may progress to cervical cancer. Highly efficacious HPV vaccines have been available since 2006, yet uptake into national programs has been slow in part due to cost. WHO guidelines call for a two-dose (0,6 month) schedule for girls 9-14 years of age. Post-hoc analyses of randomized trials have found high vaccine effectiveness following a single dose of vaccine. In order to provide additional data on the potential impact of single dose HPV vaccination in a real-world setting, we are conducting an effectiveness study among Thai schoolgirls. This is an observational study of a single dose (SD) or two doses (2D) of the bivalent HPV vaccine CERVARIX (GlaxoSmithKline plc.) administered in a school-based program to 8-9,000 Grade 8 female students in two provinces of Thailand beginning in 2018; one province is assigned the SD, and the other the standard 2D regimen. The reduction in HPV vaccine-type prevalence will be assessed in each province two and four years after vaccination by comparing HPV prevalence in urine samples obtained through cross-sectional surveys of the immunized grade cohort as they age and compared to a historical "baseline" HPV prevalence of same age students.

The evolution of herbicide-resistant weed species is a serious threat for weed control. Therefore, we need an improved understanding of how gene regulation confers herbicide resistance in order to slow the evolution of resistance. The present study analyzed differentially expressed genes after glyphosate treatment on a glyphosate-resistant Tennessee ecotype (TNR) of horseweed (Conyza canadensis), compared to a susceptible biotype (TNS). A read size of 100.2 M was sequenced on the Illumina platform and subjected to de novo assembly, resulting in 77,072 gene-level contigs, of which 32,493 were uniquely annotated by a BlastX alignment of protein sequence similarity. The most differentially expressed genes were enriched in the gene ontology (GO) term of the transmembrane transport protein. In addition, fifteen upregulated genes were identified in TNR after glyphosate treatment but were not detected in TNS. Ten of these upregulated genes were transmembrane transporter or kinase receptor proteins. Therefore, a combination of changes in gene expression among transmembrane receptor and kinase receptor proteins may be important for endowing non-target-site glyphosate-resistant C. canadensis.

Post-exposure prophylaxis (PEP) is highly effective in preventing disease progression of rabies when used in timely and appropriate manner. The key treatment for PEP is infiltration of rabies immune globulin (RIG) into lesion site after bite exposure, besides wound care and vaccination. Unfortunately, however, RIG is expensive and its supply is limited. Currently, several anti-rabies virus monoclonal antibody (mAb) products are under development as alternatives to RIG, and two recently received regulatory approval in India. In this study, fully human mAbs that recognize different rabies virus glycoprotein conformational antigenic site (II and III) were created from peripheral blood mononuclear cells of heathy vaccinated subjects. These mAbs neutralized a diverse range of lyssavirus types. As at least two anti-rabies virus mAbs are recommended for use in human PEP to ensure broad coverage against diverse lyssaviruses and to minimize possible escape variants, two most potent mAbs, NP-19-9 and 11B6, were selected to be used as cocktail treatment. These two mAbs were broadly reactive to different types of lyssaviruses isolates, and were shown to have no interference with each other. These results suggest that NP-19-9 and 11B6 are potent candidates to be used for PEP, suggesting further studies involving clinical studies in human.

INTRODUCTION: Infants with myelomeningocele are at risk for chronic kidney disease caused by neurogenic bladder dysfunction. Urodynamic evaluation plays a key role to risk stratify individuals for renal deterioration. OBJECTIVE: To present baseline urodynamic findings from the Urologic Management to Preserve Initial Renal function for young children with spina bifida (UMPIRE) protocol, to present the process that showed inadequacies of our original classification scheme, and to propose a refined definition of bladder hostility and categorization. STUDY DESIGN: The UMPIRE protocol follows a cohort of newborns with myelomeningocele at nine children's hospitals in the United States. Infants are started on clean intermittent catheterization shortly after birth. If residual volumes are low and there is no or mild hydronephrosis, catheterization is discontinued. Baseline urodynamics are obtained at or before 3 months of age to determine further management. Based on protocol-specific definitions, urodynamic studies were reviewed by the clinical site in addition to a central review team; and if necessary, by all site urologists to achieve 100% concurrence. RESULTS: We reviewed 157 newborn urodynamic studies performed between May 2015 and September 2017. Of these 157 infants, 54.8% were boys (86/157). Myelomeningocele closure was performed in-utero in 18.4% (29/157) and postnatally in 81.5% (128/157) of newborns. After primary review, reviewers agreed on overall bladder categorization in 50% (79/157) of studies. Concurrence ultimately reached 100% with further standardization of interpretation. We found that it was not possible to reliably differentiate a bladder contraction due to detrusor overactivity from a volitional voiding contraction in an infant. We revised our categorization system to group the "normal" and "safe" categories together as "low risk". Additionally, diagnosis of detrusor sphincter dyssynergia (DSD) with surface patch electrodes could not be supported by other elements of the urodynamics study. We excluded DSD from our revised high risk category. The final categorizations were high risk in 15% (23/157); intermediate risk in 61% (96/157); and low risk in 24% (38/157). CONCLUSION: We found pitfalls with our original categorization for bladder hostility. Notably, DSD could not be reliably measured with surface patch of electrodes. The effect of this change on future renal outcomes remains to be defined.

Interactive media such as video games and virtual reality (VR) provide users with lived experiences that may be dangerous or even impossible in daily life. By providing interactive experiences in highly authentic, detail-rich contexts, these technologies have demonstrated measurable success in impacting how people think, feel, and behave in the physical world. At the same time, violent interactive media content has been historically connected with a range of antisocial effects in both popular press and academic research. Extant literature has established a small-but-statistically significant effect of interactive media violence on aggressive thoughts and behaviors, which could serve as a risk factor for interpersonal violence. However, left unexplored is the seemingly paradoxical claim that under some conditions, interactive media experiences might protect against interpersonal violence. Drawing on advances in media theory and research and the evolution of interactive media content and production practices, the current manuscript suggests ways in which interactive media violence may be leveraged to lower the likelihood of real-world violence experiences. For example, research on both violent and non-violent games has found that players can (a) express guilt after committing violent acts, (b) report reflective and introspective emotional reactions during gameplay, and (c) debate the morality of their actions with others. Regarding VR, studies have demonstrated that (a) witnessing physical violence in immersive spaces led participants to take the perspective of victims and better understand their emotional state and (b) controlled exposure to traumatic or violent events can be used for treatment. Broadly, studies into video games and VR demonstrate that the impact of actions in virtual worlds transfer into the physical worlds to influence (later) attitudes and behaviors. Thus, how these experiences may be potentially harnessed for social change is a compelling and open consideration, as are side-effects of such interventions on vulnerable groups. The current manuscript summarizes emerging research perspectives (as well as their limitations) to offer insight into the potential for interactive media violence to protect against real-world violence victimization and perpetration.

OBJECTIVE: To advance public health support for the U.S. Department of Housing and Urban Development's smoke-free rule, the Centers for Disease Control and Prevention collaborated with the Georgia Institute of Technology to develop a geospatial mapping tool. The objective was to create a tool state and local public health agencies could use to tailor smoke-free educational materials and cessation interventions for specific public housing development resident populations. RESULTS: The resulting "Extinguish Tool" includes an interactive map of U.S. public housing developments (PHDs) and healthcare facilities that provides detailed information on individual PHDs, their proximity to existing healthcare facilities, and the demographic characteristics of residents. The tool also estimates the number of PHD residents who smoke cigarettes and calculates crude estimates of the potential economic benefits of providing cessation interventions to these residents. The geospatial mapping tool project serves as an example of a collaborative and innovative public health approach to protecting the health and well-being of the nation's two million public housing residents, including 760,000 children, from the harms of tobacco smoking and secondhand smoke exposure in the places where they live, play, and gather.

Respirable crystalline silica (RCS) produced in mining and construction industries can cause life-threatening diseases such as silicosis, lung cancer, and chronic obstructive pulmonary disease (COPD). These diseases could be more effectively treated and prevented if RCS-related biomarkers were identified and measured at an early stage of disease progression, which makes development of a point of care test (POCT) platform extremely desirable for early diagnosis. In this work, a new, highly sensitive lab on a chip (LOC) immunoassay has been designed, developed, and characterized for tumor necrosis factor alpha (TNF-alpha), a protein biomarker that causes lung inflammation due to RCS exposure. The designed LOC device is composed of four reservoirs for sample, enzyme conjugated detection antibody, wash buffer, and chemiluminescence substrate in liquid form, along with three spiral reaction chambers for test, positive control, and negative control. All reservoirs and spiral microchannels were connected in series and designed to perform sequential delivery of immunoassay reagents with minimal user intervention. The developed LOC measured TNF-alpha concentrations as low as 16 pg/mL in plasma from RCS-exposed rats and also had a limit of detection (LOD) of 0.5 pg/mL in spiked artificial serum. In addition, the analysis time was drastically reduced to about 30 min, as opposed to hours in conventional methods. Successful implementation of a highly sensitive, chemiluminescence-based immunoassay on a preloaded LOC with proper quality control, as reported in this work, can pave the way toward developing a new rapid POCT platform for in-field clinical diagnosis.

Animal models suggest that gut microbiota contribute to obesity; however, a consistent taxonomic signature of obesity has yet to be identified in humans. We examined whether a taxonomic signature of obesity is present across two independent study populations. We assessed gut microbiome from stool for 599 adults, by 16S rRNA gene sequencing. We compared gut microbiome diversity, overall composition, and individual taxon abundance for obese (BMI >/= 30 kg/m(2)), overweight (25 </= BMI < 30), and healthy-weight participants (18.5 </= BMI < 25). We found that gut species richness was reduced (p = 0.04), and overall composition altered (p = 0.04), in obese (but not overweight) compared to healthy-weight participants. Obesity was characterized by increased abundance of class Bacilli and its families Streptococcaceae and Lactobacillaceae, and decreased abundance of several groups within class Clostridia, including Christensenellaceae, Clostridiaceae, and Dehalobacteriaceae (q < 0.05). These findings were consistent across two independent study populations. When random forest models were trained on one population and tested on the other as well as a previously published dataset, accuracy of obesity prediction was good (~70%). Our large study identified a strong and consistent taxonomic signature of obesity. Though our study is cross-sectional and causality cannot be determined, identification of microbes associated with obesity can potentially provide targets for obesity prevention and treatment.

BACKGROUND: Colorectal cancer is a heterogeneous disease arising from at least two precursors-the conventional adenoma (CA) and the serrated polyp. We and others have previously shown a relationship between the human gut microbiota and colorectal cancer; however, its relationship to the different early precursors of colorectal cancer is understudied. We tested, for the first time, the relationship of the gut microbiota to specific colorectal polyp types. RESULTS: Gut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples. Participants were categorized as CA cases (n = 144), serrated polyp cases (n = 73), or polyp-free controls (n = 323). CA cases were further classified as proximal (n = 87) or distal (n = 55) and as non-advanced (n = 121) or advanced (n = 22). Serrated polyp cases were further classified as hyperplastic polyp (HP; n = 40) or sessile serrated adenoma (SSA; n = 33). We compared gut microbiota diversity, overall composition, and normalized taxon abundance among these groups. CA cases had lower species richness in stool than controls (p = 0.03); in particular, this association was strongest for advanced CA cases (p = 0.004). In relation to overall microbiota composition, only distal or advanced CA cases differed significantly from controls (p = 0.02 and p = 0.002). In taxon-based analysis, stool of CA cases was depleted in a network of Clostridia operational taxonomic units from families Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and enriched in the classes Bacilli and Gammaproteobacteria, order Enterobacteriales, and genera Actinomyces and Streptococcus (all q < 0.10). SSA and HP cases did not differ in diversity or composition from controls, though sample size for these groups was small. Few taxa were differentially abundant between HP cases or SSA cases and controls; among them, class Erysipelotrichi was depleted in SSA cases. CONCLUSIONS: Our results indicate that gut microbes may play a role in the early stages of colorectal carcinogenesis through the development of CAs. Findings may have implications for developing colorectal cancer prevention therapies targeting early microbial drivers of colorectal carcinogenesis.

Coccidioidomycosis (CM), a serious and life threatening fungal infection endemic to arid regions of western United States and Mexico, can be challenging to diagnose in a timely manner. Commercially developed enzyme immunoassays (EIA; Meridian Biosciences and Immuno-Mycologics (IMMY)) have provided a faster, simpler means for serodiagnosis; however, independent evaluations have questioned EIA specificity, particularly IgM-positive/IgG-negative results. This study was conducted to evaluate EIA specificity in persons not likely to have been exposed to Coccidioides sp. residing in non-endemic Puerto Rico (PR; n=534) compared to sera from blood bank donors residing in endemic Arizona (AZ; n=1218). Upon comparing serum reactivity between PR and AZ, the Meridian EIA showed a significant difference in IgG-reactivity (0.37% vs. 3.6%, p<0.001), but not in IgM-reactivity (3.4% vs. 2.4%). No IgM/IgG-reactive sera were detected in PR sera compared to 7 (0.57%) from AZ. Similar results were observed using the IMMY EIA, although significantly (p=0.03) fewer IgM-reactive sera were observed from AZ, compared to Meridian EIA. EIA-reactive sera were also evaluated by immunodiffusion before and after 3-4-fold concentration of the sera. These results demonstrate that elevated IgG EIA-reactivity is present in sera from healthy individuals in endemic regions and that IgM EIA-reactivity observed in sera from individuals residing outside the endemic region is most likely false. Other criteria, including clinical and microbiological evaluation, should be taken into account when interpreting results from surveillance studies and other reporting measures.

OBJECTIVE: To assess the relationship between secondhand smoke (SHS) exposure and disease severity among children hospitalized with community-acquired pneumonia (CAP). STUDY DESIGN: Children hospitalized with clinical and radiographic CAP were enrolled between January 1, 2010, and June 30, 2012 at 3 hospitals in Tennessee and Utah as part of the Centers for Disease Control and Prevention's Etiology of Pneumonia in the Community study. Household SHS exposure was defined based on the number of smokers in the child's home. Outcomes included hospital length of stay, intensive care unit admission, and mechanical ventilation. Proportional hazards and logistic regression models were used to assess associations between SHS exposure and outcomes. All models were adjusted for age, sex, race/ethnicity, household education level, government insurance, comorbidities, enrollment site, year, and season. RESULTS: Of the 2219 children included in the study, SHS exposure was reported in 785 (35.4%), including 325 (14.8%) with ≥2 smokers in the home. Compared with nonexposed children, the children exposed to ≥2 smokers had longer length of stay (median, 70.4 hours vs 64.4 hours; adjusted hazard ratio, 0.85; 95% CI, 0.75-0.97) and were more likely to receive intensive care (25.2% vs 20.9%; aOR, 1.44; 95% CI, 1.05-1.96), but not mechanical ventilation. Outcomes in children exposed to only 1 household smoker were similar to those in nonexposed children. CONCLUSION: Children hospitalized with CAP from households with ≥2 smokers had a longer length of stay and were more likely to require intensive care compared with children from households with no smokers, suggesting that they experienced greater pneumonia severity.

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25.7 million adults (age 15-99 years) and 75 000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. FUNDING: Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).

One of the difficulties of isolating Cryptococcus neoformans and Cryptococcus gattii from environmental samples is the abundant overgrowth of other yeast and mold species that occurs on the plates. Here we report the application of benomyl to Guizotia abyssinica seed extract growth medium to improve the isolation of C. neoformans and C. gattii from environmental samples. We validated this medium by recovering C. neoformans and C. gattii from convenience soils and swabs from a region of the United States where these yeasts are endemic.