Death Index Research Articles

Abstract 830: Michigan cancer and research on the environment study (MI-CARES) cohort: Baseline methods and participant characteristics

Abstract Michigan has a long history of adverse environmental exposures, many of which are still ongoing, like the Flint water crisis, extreme air pollution burden, and widespread PFAS exposure. Michigan is also home to a diverse population of Latinx, Black, White, and Middle Eastern/North African (MENA) Americans. Because minority populations are underrepresented in environment and cancer research despite being at greater risk of being exposed to environmental hazards and having worse cancer outcomes, Michigan is uniquely positioned for studying the associations between environmental exposures and cancer risk. In June 2022, the Michigan Cancer and Research on the Environment Study (MI-CARES) began recruitment with a goal of establishing a cohort of over 100,000 Michiganders to examine these associations. Any Michigander aged 18-49 is eligible to enroll in MI-CARES. By focusing on this age range, we will capture exposures during important windows of susceptibility prior to the onset of most cancers.While recruitment is open to all state-wide, efforts are focused on six environmental injustice hotspots, identified using the MiEJScreen tool, a relative summary score capturing pollution burden and population vulnerability: the metro areas of Kalamazoo, Grand Rapids, Flint, Lansing, Detroit, and Bay City-Saginaw.MI-CARES will enroll equal numbers of Black, Latinx, MENA, and White participants. To support participation in diverse communities, study materials are available in Arabic, English, and Spanish. MI-CARES has employed a multifaceted community engagement strategy and is recruiting from these communities directly and with the help of community partners. An incentive of $10 is also provided to participants who successfully complete the questionnaire.To democratize participation, MI-CARES enrollment can be completely remote, but in-person and paper-based enrollment is available. Enrollment includes a baseline questionnaire, consent for data linkage, and annual follow-up surveys. Participants are also asked to provide saliva and blood spot samples via a mailed at-home biospecimen collection kit. Biospecimens will be analyzed for environmental exposures like heavy metals and for intermediate cancer markers including inflammation, cellular aging, immune function, and altered metabolism. Participant data will be linked to neighborhood-level exposure databases, administrative databases like cancer registries and death indices, and to the Michigan Neonatal Biobank. More than 4,000 Michiganders have enrolled in MI-CARES. Data on initial cohort members including environmental exposure history and demographic characteristics will be presented. MI-CARES is part of the Cohorts for Environmental Exposures and Cancer Risk (CEECR) consortium, which is funded by the National Cancer Institute and the National Institute for Environmental Health Sciences. Citation Format: Lilah Khoja, Maxwell Salvatore, Minh Tung Phung, Isabella De Sa, Heatherlun Uphold, Justin Colacino, Alison M. Mondul, Bhramar Mukherjee, Dana Dolinoy, Celeste Leigh Pearce. Michigan cancer and research on the environment study (MI-CARES) cohort: Baseline methods and participant characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 830.

Survival of primary liver cancer for people from culturally and linguistically diverse backgrounds in Australia

BackgroundSurvival for Primary Liver Cancer (PLC) has been investigated in Australia, but limited work has been conducted on the burden for people with different socioeconomic status, region of residence, causes of PLC, and culturally and linguistically diverse (CALD) backgrounds. This study aimed to cover this gap in the literature by investigating PLC survival with the aforementioned factors. MethodsThis study linked four administrative datasets: Victorian Cancer Registry, Admitted Episodes Dataset, Emergency Minimum Dataset, and Death Index. The cohort was all cases with a PLC notification within the Victorian Cancer Registry between 01/01/2008 and 01/01/2016. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test was used to compare the difference in survival between subgroups. The Cox proportional hazard model was used to explore factors associated with PLC survival. ResultsThe 1-, 3- and 5-year survival rates were 50.0%, 28.1% and 20.6%, respectively, with a median survival of 12.0 months (95% confidence interval (CI): 11.0 – 12.9 months). Higher survival was associated with younger age, hepatocellular carcinoma, and higher socio-economic status. People born in Asian, African, and American regions had higher survival than those born in Australia and New Zealand. Cases with viral hepatitis as an identified aetiology had higher survival than those whose PLC was related to alcohol consumption (hazard ratio=1.52, 95% CI: 1.19 – 1.96), diabetes and fatty liver disease (hazard ratio=1.35, 95% CI: 1.08 – 1.68). ConclusionSurvival outcomes for people diagnosed with PLC were still poor and affected by many factors. Asian and African cases had better survival than Australian and New Zealand patients as PLC in Asian and African cases was mostly caused by viral hepatitis. Metropolitan areas were associated with a higher survival than rural areas, not only due to accessibility to surveillance and healthcare services but also because the majority of overseas-born patients reside in metropolitan areas.

Dynamics of suicidal frequency changes within the Poland rail system - an attempt of epidemiological analyzes.

The analysis presented in the article is the first study of suicide on railway tracks in Poland. An epidemiological assessment was conducted, study type: case series, population-based with use of the data from the National Police Headquarters. The rates of railway suicides in Poland in the years 2007-2018 were compared to the overall number of suicides in Poland and in the Europe. In 2007-2018, the average share of deaths by railway suicide in the overall number of suicides committed in Poland amounted to 2.06%. Between the years: 1999 -2018 there is a growing number of railway suicide attempts and railway suicide attempts without deaths. Since 2012, an increase of suicide attempts on railway tracks, along with a constant number of suicide deaths, has been observed. In 2017 - 2018, throwing oneself under a train to end one's lifewas the third most commonly chosen method in Poland. Although it accounted for only a small percentage of all methods of suicide, it was chosen relatively more often than in other European countries. Poland belongs to a small group of European countries where the number of deaths by suicide has displayed an upward tendency in the course of 20 years. There is a growing number of unsuccessful railway suicide attempts. The index of deaths on railway tracks in Poland, was considerably higher than the average index for the EU.

Критические акушерские состояния в Дальневосточном федеральном округе в пандемию COVID-19 и до эпидемии

Study Objective. To assess the structure and indicators of critical obstetric conditions and maternal deaths in the Far East Federal District of Russia before (2019) and during (2020) the COVID-19 pandemic. Study Design: Retrospective comparative analysis. Material and methods. We have reviewed medical records on near misses (NM) and maternal deaths (MD) for 2019 (194 and 17, respectively) and 2020 (207 and 19, respectively). Descriptive statistics, cross tables analysis with evaluation of the Pearson’s chi-square and p-value, odds ratio calculation at 95%CI were used for mathematic data processing. Study Results. In 2019 and 2020, maternal death rate was 18.7 and 21.1 per 100,000 live births, respectively. Obstetric causes of maternal deaths demonstrated statistically significant reduction during the COVID-19 pandemic (2020) (26.3% vs 76.5% in 2019, р < 0.05); the ratio of life-threatening conditions (NMs and MDs) grew from 2.3 to 2.5; and COC (NM) coefficient soared from 2.1 to 2.3 per 100,000 life births. Reduction in the survival index from 11.4 to 10.9 and increase in the death index from 8.1% to 8.4% can evidence poorer quality of medical care. Conclusion. Analysis of trends and indicators of the critical obstetric conditions allows evaluating the system of organisational and medical measures, revealing issues with obstetrics services and finding additional resources to reduce maternal morbidity and mortality during the emergency situation caused by COVID-19. Кeywords: critical obstetric conditions, near miss, maternal deaths, COVID-19.

Multidimensional comparative analysis of the number of deaths in Europe between 2018–2021 in terms of economic security

The study concerned a multidimensional comparative analysis of the number of deaths in 30 European countries between 2018-2021, also by age groups and type of vaccination in Poland in 2021 in terms of the impact of the COVID-19 pandemic and economic security. The data for the research was obtained from the websites of Eurostat and the Central Statistical Office. They were grouped and sorted from largest to smallest. In order to achieve the aim of the study, the death indices were calculated and analyzed. The obtained test results are included in bar charts. The article ends with a summary and final conclusions.

Abstract 8917: Ankle-Brachial Index and Risk of Sudden Cardiac Death in the Community: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Sudden cardiac death (SCD) is an important public health problem. About 356,000 people suffer SCD in the U.S., accounting for 15% of all deaths. The ankle-brachial index (ABI) is a simple, non-invasive measure of subclinical atherosclerosis. The aim of this study was to determine the relation between ABI and SCD in a middle-aged biracial general population. Methods: All ARIC (Atherosclerosis Risk in Communities) study subjects with a documented ABI measurement between 1987 and 1989 were included in the study. ABI was categorized as abnormal (≤0.9), borderline (0.9-1), normal [1-1.4], and non-compressible (>1.4). SCD was defined as a sudden pulseless condition presumed to be caused by a ventricular tachyarrhythmia in a previously stable individual. All SCD cases were adjudicated by a committee of cardiac electrophysiologists, cardiologists, and internists. Results: Of the 15,135 participants followed for a median of 23.5 years, 558 (3.7%) developed SCD (1.96 cases per 1000 person-years). Abnormal or borderline ABIs were associated with an elevated risk of SCD (HRs with 95 % CIs 2.27 [1.64-3.14] and 1.52 [1.17-1.96], respectively) in comparison to normal ABI. The association between abnormal ABI and SCD remained significant after adjustment for traditional cardiovascular risk factors, but not for borderline ABI (HR 1.63 [1.15-2.32] and 1.24 [0.94-1.63]) (Table). Conclusions: Abnormal ABI is independently associated with risk of SCD in a biracial general population. ABI could be incorporated into a future risk SCD prediction model.

Higher mortality in frail elderly with atrial fibrillation using oral anticoagulants

Abstract Background/Introduction Frail older persons with falls are often undertreated for atrial fibrillation (AF) due to fear of bleeding complications of oral anticoagulants (OAC). However, the safety of OAC use in frail elderly with AF and falls is not investigated extensively. Purpose The aim of the study was to investigate whether frail older persons with falls and OAC for AF have more bleeding complications than patients without OAC and to investigate the association between frailty, OAC therapy (including bleeding complications), and mortality. Methods This observational study included frail patients aged 65 years or older who were evaluated for falls between November 2011 and December 2019. Patients using OAC for AF were compared with similar patients without using OAC. Primary outcomes were death, major bleeding and intracranial bleeding. Secondary outcomes were frailty measured by the Frailty Index and cause of death. Results Of the 645 included patients, 132 had AF and used OAC. Patients with AF were more often severely frail (67% vs. 47%, p<0.001) and had a higher mortality during follow up (39% vs. 27%, p=0.005). Patients using OAC had a higher mortality risk compared to the patients without OAC (crude analysis Hazard Ratio (HR) 1.7 (95% confidence interval (CI) 1.3–2.4), p=0.001; after adjustment for age, gender, and frailty index HR 1.4 (95% CI 0.99–1.9) p=0.056). No differences were found in the incidence of major bleedings (10% vs. 7%, p=0.204) or intracranial bleedings (5% vs. 4%, p=0.739) in both groups. The causes of death were similar in both groups, also the incidence of fatal bleedings did not differ (5% vs 7%, p=0.758). Conclusions Elderly with falls and AF using OAC are frailer and have a tendency to a higher mortality risk than patients without AF. These frail elderly patients with falls had no more bleeding complications during OAC treatment than comparable patients without OAC. Therefore, withholding OAC out of fear for major bleeding complications is not justified. It is unclear why elderly persons with AF and OAC are frailer and die sooner, since the incidence of major bleedings and fatal bleedings is equal. Further research should focus why older frail persons with AF are more prone to die. Funding Acknowledgement Type of funding sources: None.

Developmental intestinal microbiome alterations in canine fading puppy syndrome: a prospective observational study

Fading puppy syndrome (FPS) is a fatal condition in neonatal dogs. Intestinal microbial alterations, although never investigated, may be involved in its pathophysiology. The study examined the occurrence of FPS and its associations with dam, puppy, and husbandry characteristics, compared the intestinal microbial diversity of healthy puppies and those with FPS, and examined whether intestinal microbiomes are predictive of FPS. Day 1 and 8 post-partum (PP) rectal swabs were collected from healthy puppies and puppies which later developed FPS. Microbial compositional structure, including alpha and beta diversities and relative abundance of specific taxa were compared between groups, and microbial data was applied to a machine-learning model to assess the predictive performance of microbial indices of FPS or death. FPS occurred in 22/165 puppies (13%), with a 100% mortality rate. FPS was associated (P < 0.001) with decreased Day 1 PP puppy activity. Day 1 (P = 0.003) and 8 (P = 0.005) PP rectal beta diversities were different in puppies with FPS vs healthy ones. Increased Proteobacteria/Firmicutes ratio, increased relative abundance of Pasteurellaceae, and decreased relative abundance of Clostridia and Enterococcus were associated with FPS. A machine-learning model showed that Day 1 PP rectal microbiome composition accurately predicted FPS-related death. We found that specific rectal microbial phenotypes are associated with FPS, reflecting the significant role of microbiome alterations in this phenomenon. These findings may serve as useful microbial indices for early diagnosis of puppies at risk of FPS and may provide specific therapeutic targets.

COVID-19 and stock exchange return variation: empirical evidences from econometric estimation.

This research looked at the effects of COVID-19 on a number of the world’s most important stock exchanges, as well as the empirical relation between the COVID-19 wave and stock market volatility. In order to plan proper portfolio diversification in international financial markets, researchers must examine COVID-19 anxiety in relation to stock market volatility. The stock market volatility connected with the COVID-19 pandemic was measured using AR(1)-GARCH(1,1). COVID-19 fear, according to our research, is the ultimate driver of public attention and stock market volatility. The findings show that throughout the pandemic, stock market performance and GDP growth both declined significantly due to average increases. Furthermore, a 1% increase in COVID-19 causes a 0.8% and 0.56% decline in stock return and GDP, respectively. The stock market, on the other hand, showed a slight movement in GDP growth. Furthermore, the COVID-19 pandemic reported cases index, death index, and global panic index all influenced public perceptions of purchasing and selling. As a result, rather than investing in stocks, it is recommended that you invest in gold. The research also makes policy recommendations for important stakeholders. We look to examine how stock returns respond dynamically to unanticipated changes in the COVID-19 scenarios, as well as the uncertainty that comes with a pandemic. Using daily data from Canada and the USA, we conclude that a spike in COVID-19 instances has a negative impact on the stock market in general. Furthermore, in both the increase and decline scenarios in Canada, the stock return reactions are asymmetric. The disparity is due to the unfavorable impact of the pandemic’s unpredictability. We also discovered that uncertainty had a negative impact on the US stock market. The magnitude, however, is insignificant.

The nexus between COVID-19 fear and stock market volatility

This study described an empirical link between COVID-19 fear and stock market volatility. Studying COVID-19 fear with stock market volatility is crucial for planning adequate portfolio diversification in international financial markets. The study used AR (1) – GARCH (1,1) to measure stock market volatility associated with the COVID-19 pandemic. Our findings suggest that COVID-19 fear is the ultimate cause driving public attention and stock market volatility. The results demonstrate that stock market performance and GDP growth decreased significantly through average increases during the pandemic. Further, with a 1% increase in COVID-19 cases, the stock return and GDP decreased by 0.8%, 0.56%, respectively. However, GDP growth demonstrated a slight movement with stock exchange. Moreover, public attention to the attitude of buying or selling was highly dependent on the COVID-19 pandemic reported cases index, death index, and global fear index. Consequently, investment in the gold market, rather than in the stock market, is recommended. The study also suggests policy implications for key stakeholders.

Thrombospondin-1/CD47 signaling modulates transmembrane cation conductance, survival, and deformability of human red blood cells

BackgroundThrombospondin-1 (TSP-1), a Ca2+-binding trimeric glycoprotein secreted by multiple cell types, has been implicated in the pathophysiology of several clinical conditions. Signaling involving TSP-1, through its cognate receptor CD47, orchestrates a wide array of cellular functions including cytoskeletal organization, migration, cell-cell interaction, cell proliferation, autophagy, and apoptosis. In the present study, we investigated the impact of TSP-1/CD47 signaling on Ca2+ dynamics, survival, and deformability of human red blood cells (RBCs).MethodsWhole-cell patch-clamp was employed to examine transmembrane cation conductance. RBC intracellular Ca2+ levels and multiple indices of RBC cell death were determined using cytofluorometry analysis. RBC morphology and microvesiculation were examined using imaging flow cytometry. RBC deformability was measured using laser-assisted optical rotational cell analyzer.ResultsExposure of RBCs to recombinant human TSP-1 significantly increased RBC intracellular Ca2+ levels. As judged by electrophysiology experiments, TSP-1 treatment elicited an amiloride-sensitive inward current alluding to a possible Ca2+ influx via non-selective cation channels. Exogenous TSP-1 promoted microparticle shedding as well as enhancing Ca2+- and nitric oxide-mediated RBC cell death. Monoclonal (mouse IgG1) antibody-mediated CD47 ligation using 1F7 recapitulated the cell death-inducing effects of TSP-1. Furthermore, TSP-1 treatment altered RBC cell shape and stiffness (maximum elongation index).ConclusionsTaken together, our data unravel a new role for TSP-1/CD47 signaling in mediating Ca2+ influx into RBCs, a mechanism potentially contributing to their dysfunction in a variety of systemic diseases.FKY5xz95WsHn6abiyZ6BGLVideo abstract

Synthesis and Bioactivity of Quinone Mono- and Dioxime Salts

Eliminating all kinds of harmful organisms is an important task in agriculture, food production, and human life. Quinone oximes and their salts are good bioactive compounds to attain this aim. The alkali metal salts of quinone mono- and dioxime have been synthesized by the reaction of the corresponding quinone oxime with alkali metal hydroxide. The divalent metal salts have been obtained in two stages. The first stage is the synthesis of the sodium salt of the quinone oxime. The second step is the reaction of the latter with a divalent metal salt. Copper and zinc salts of [(4-oxocyclohexa-2,5-dien-1-ylidene)amino]oxidanide have the highest insecticidal activity against the housefly and rice weevil. The death index is 90–100%. Copper {[2-methyl-4-oxo-5-(propan-2-yl)cyclohexa-2,5-dien-1-ylidene]amino}oxidanide shows good activity against Phytophthora infestans. Inhibition of the growth and development of the Phytophthora infestans is 80%.

Genetic and Reproductive State Assessment of Ulmus pumila and U. suberosa Invasive Populations in the Dnieper Steppe under Climate Change

The degree of intraspecific genetic polymorphism and heterozygosity, the germinal death, viability of seeds, and the cytogenetic state of vegetative Ulmus pumila and U. suberosa meristems were analyzed for determining the mechanisms of plant population invasiveness in the steppe Dnieper region under climate changes. The studied U. pumila population were different in terms of germinal (embryonic) death, seed viability and seed productivity. Populations grown under more favorable environmental conditions had the best reproductive, physiological and genetic conditions. For the majority of used microsatellite loci, population studies were characterized by a relatively low level of genetic variability, an excess of homozygous genotypes and a deficiency of heterozygotes, which indicated a certain level of inbreeding of the analyzed plants. The highest deficiency of heterozygotes was found in U. pumila populations with high stand density and significant indices of germinal seed loss; smaller deficits were in populations with a larger area and low stand density and, accordingly, low rates of germinal death. The low index of chromosomal rearrangements in the vegetative meristems also confirmed an insignificant level of genetic variability and the probable absence of hybridization and genetic homeostasis in U. pumila. The U. suberosa population was characterized by increased indices of germinal death, seed damage and low seed productivity, which correlated with an excess of homozygous genotypes. All U. suberosa specimens were monomorphic by the microsatellite loci. In general, by genetic and reproductive indices, seed reproduction and distribution of U. pumila in the steppe Dnieper region is not significantly limited under climate change. At the same time, seed reproduction of U. suberosa may be limited.

Incorporation of AuNP-PLL nanocomplexes in DPSC: a new tool for 3D analysis in pulp regeneration.

To assess the viability of dental pulp stem cells loaded with gold nanoparticles complexed with poly (L-lysine) (AuNP-PLL) and to track the cellular behavior in a 3D analysis by micro-CT. DPSC (dental pulp stem cells) were cultured and incorporated with AuNP-PLL (0.2mg/ml) and assessed for cell viability (24h, 48h, and 72h) using MTS assay. Apoptosis/cell death index and cell cycle were analyzed by propidium iodide. AuNP-PLL-RITC were used for observation in confocal microscopy and quantification of the incorporation rates. Cells were also suspended in agarose and analyzed three-dimensionally in μCT, assessing their radiopacity. Quantitative data (cell viability and apoptosis) were analyzed by t test (p < 0.05). AuNP-PLL labeling did not affect cellular viability in any of the periods analyzed nor interfered with the apoptosis index of DPSC. AuNP-PLL nanocomplexes were identified in the cytoplasm of cells by immunofluorescence, mainly in the perinuclear region. The observedincorporation rate was 98%. Micro-CT analysis has shown that incorporated cells are now visible using x-ray, with a clear increase in radiopacity when compared to the control group (non-incorporated cells). These results indicate that it is possible to incorporate AuNP-PLL complex into DPSC and track the cells by using μCT; furthermore, this incorporation of 0.2mg/ml of AuNP-PLL does not interfere in the DPSC basic behavior. This methodology can be a useful tool for cellular labeling to observe cell behavior and their interaction with scaffolds in a 3D manner, opening an array of new approaches in regenerative endodontics.

Structural stigma and all-cause mortality among sexual minorities: Differences by sexual behavior?

Using updated data from the General Social Survey/National Death Index (GSS/NDI) study, we examined whether the relationship between structural stigma—measured by aggregating 4 items assessing prejudice towards homosexuality to the community level—and all-cause mortality is present among gay men/lesbian women. Our hypothesis is based on emerging evidence that indicators of structural stigma specific to homosexuality, such as those used in the GSS/NDI, uniquely predict health outcomes among this group. Because the GSS/NDI lacked an identity-based measure of sexual orientation, we tested our hypothesis by employing a strategy that has a relatively high degree of sensitivity and specificity for ascertaining individuals most likely to identify as gay or lesbian: restricting analyses to individuals who reported same-sex sexual partners in the past year. We compared this approach against an alternative strategy, which has weaker specificity for identifying gay men/lesbian women: restricting analyses to individuals who reported any lifetime same-sex sexual behaviors. After controlling for 6 individual-level factors and fixed effects of survey year, structural stigma was associated with mortality among individuals who reported past-year same-sex sexual partners (HR = 1.95, 95% CI: 1.14, 3.31). Further, there was a dose-response relationship with mortality in this group, such that those residing in communities in the highest quartile of structural stigma had the greatest mortality risk, controlling for these same factors (HR = 2.12, 95% CI: 1.03, 4.38). In sensitivity analyses, the effect size for structural stigma ranged from 1.54 to 2.30, indicating a consistent, but small-to-moderate, effect. In contrast, no association between structural stigma and mortality was observed among respondents who reported lifetime same-sex sexual partners, nor among those reporting only opposite-sex sexual partners. This analysis therefore delimits potential boundary conditions of the association between structural stigma related to same-sex sexuality and all-cause mortality, highlighting the conditions under which this association is (and is not) observed.

Is one dose of human papillomavirus vaccine as effective as three?: A national cohort analysis

AimProphylactic human papillomavirus (HPV) vaccines are highly effective at preventing pre–cancerous cervical lesions when given in a three–dose schedule. Some post–hoc trial data suggest that one dose prevents HPV infection. If one dose could prevent pre–cancerous cervical lesions, then global cervical cancer prevention would be greatly facilitated. We assessed the effectiveness of quadrivalent HPV vaccine by number of doses against cervical intraepithelial neoplasia (CIN) 2 or 3/adenocarcinoma–in–situ (AIS)/cancer in Australia up to seven years post vaccination. MethodsWe linked registry data from all 8 jurisdictional cervical screening registers, with the national HPV vaccination register, death index and cancer registers for all Australian women aged 15 or under when eligible for vaccine who screened between April 2007 (when vaccination commenced) and 31 December 2014. We performed Cox proportional hazard regression, adjusted a priori for age, socioeconomic status, and area of residence, to estimate hazard ratios of histologically confirmed CIN2/CIN3/AIS/cancer. ResultsWe included 250,648 women: 48,845 (19·5%) unvaccinated, 174,995 (69·8%) had received three doses, 18,190 (7·3%) two doses and 8,618 (3·4%) one dose. The adjusted hazard ratio was significantly lower for all dose groups compared to unvaccinated women (1 dose 0·65 (95%CI 0·52–0·81), 2 doses 0·61 (0·52–0·72) and 3 doses 0·59 (0·54–0·65).) With adjustment for age at vaccination amongst the vaccinated group, the adjusted hazard ratios for one dose and two dose recipients were comparable to three dose recipients (one dose 1.01 (95%CI 0.81–1.26), two doses 1.00 (0.85–1.17).) Multiple sensitivity analyses, including use of different dose assignment methods, produced consistent findings. Comparison with a historical cohort of age matched women showed that the result was not due to herd protection alone. ConclusionsOne dose had comparable effectiveness as two or three doses in preventing high–grade disease in a high coverage setting. These findings support the hypothesis that one dose vaccination may be a viable strategy when working towards the global elimination of cervical cancer.

Using health-related quality of life and treatment measures to predict 10-year mortality in older survivors of early stage breast cancer.

e21548 Background: Older women make up the growing majority of breast cancer (BC) survivors. Guideline BC treatments are known contributors to long-term survival, and health-related quality of life (HRQOL) is emerging as not only an important outcome in survivorship care but also as a factor thought to influence mortality. However, prognostic models that include HRQOL alongside BC treatment measures are lacking. We aimed to develop a 10-year mortality risk score based on a priori chosen treatment and HRQOL variables. Methods: We studied 660 women ≥65-years old diagnosed with stage I-IIIA primary breast cancer in years 1997-1999. Data from medical and psychosocial domains were collected over 10 years from interviews, medical records, and death indexes. BC treatment variables included receipt of definitive locoregional surgery +/- radiation, chemotherapy, and tamoxifen. HRQOL variables included physical function [10-item Physical Function Index (PFI-10) from the Medical Outcomes Study Short Form-36 (MOS SF-36)]; mental health [5-item Mental Health Index (MHI-5) from the MOS SF-36]; and social support [8-item modified MOS Social Support Scale (mMOS-SSS)]. We used penalized logistic regression models to develop a 10-year mortality risk score, and investigated its discrimination (c-statistic) and calibration (observed versus predicted mortality using the Hosmer-Lemeshow (HL) test). Results: Mortality though 10-years of follow-up was 34.8% (230 of 660 women). The c-statistic of a risk score using only age, number of comorbidities, stage of BC, and BC treatment was 0.71. The c-statistic increased to 0.74 with the addition of HRQOL measures and showed good calibration (p = 0.72 from HL test). Physical function and mental health had strong independent associations with mortality (women with high PFI-10: OR 0.63, 95% CI 0.43, 0.92; women with high MHI-5: OR 0.57, 95% CI 0.39, 0.85). Conclusions: In older early stage breast cancer survivors, our risk score combining HRQOL with treatment measures showed good discrimination and calibration. HRQOL is independently associated with 10-year mortality and adds predictive ability to age, comorbidity, stage of BC, and BC treatment.

Reducing liberal red blood cell transfusions at an academic medical center

Educational and computerized interventions have been shown to reduce red blood cell (RBC) transfusion rates, yet controversy remains surrounding the optimal strategy needed to achieve sustained reductions in liberal transfusions. The purpose of this study was to assess the impact of clinician decision support (CDS) along with targeted education on liberal RBC utilization to four high-utilizing service lines compared with no education to control service lines across an academic medical center. Clinical data along with associated hemoglobin levels at the time of all transfusion orders between April 2014 and December 2015 were obtained via retrospective chart review. The primary outcome was the change in the rate of liberal RBC transfusion orders (defined as any RBC transfusion when the hemoglobin level is >7.0 g/dL). Secondary outcomes included the annual projected reduction in the number of transfusions and the associated decrease in cost due to these changes as well as length of stay (LOS) and death index. These measures were compared between the 12 months prior to the initiative and the 9-month postintervention period. Liberal RBC utilization decreased from 13.4 to 10.0 units per 100 patient discharges (p = 0.002) across the institution, resulting in a projected 12-month savings of $720,360. The mean LOS and the death index did not differ significantly in the postintervention period. Targeted education combined with the incorporation of CDS at the time of order entry resulted in significant reductions in the incidence of liberal RBC utilization without adversely impacting inpatient care, whereas control service lines exposed only to CDS had no change in transfusion habits.

Abstract 260: Systemic Loss of p62 Reduces Pressure Overload Induced Cardiac Hypertrophy, Dysfunction and Apoptosis

Introduction: p62 is a pleiotropic protein with defined roles in TNFα signaling, protein aggregate formation, and protein degradation processes. Current data suggest that p62 is a stress-response protein, with increased protein levels reported in TAC, MI, I/R, and protein aggregation models of cardiac disease. To date, there has been little study on the gain- or loss- of p62 function in cardiomyocyte/cardiac pathology. Our preliminary data found that adenoviral overexpression of p62 caused cardiomyocyte hypertrophy and cytotoxicity and that p62 was upregulated by pressure-overload stress. Hypothesis: Loss of p62 will be cardioprotective against pressure-overload pathology. Methods: Systemic p62 knockout mice underwent sham or transverse-aortic constriction surgery and were studied longitudinally to 8 weeks post-surgery by echocardiography. Results: Hearts from p62-null mice had significantly preserved cardiac function (%Fractional Shortening) over wild-type controls. p62-deficient mice had significantly less cardiac hypertrophy (heart weight/body weight ratios and myofiber cross-sectional areas) and showed no chamber dilation (LVED) in response to pressure-overload stress, unlike wild-types. Hearts from wild-type mice showed pronounced fibrotic remodeling and induction of apoptosis (TUNEL), while p62 knockouts had significantly less collagen staining and no evidence of apoptotic stimulation. Overexpression of p62 in rat neonatal cardiomyocytes significantly inhibited proteasomal catalytic activities (&gt;50%) and showed increased indices of cardiomyocyte cell death. Conclusion: Our data show that induction of p62 is deleterious in vitro and that loss of p62 imparts cardioprotection against hemodynamic stress in vivo . The beneficial phenotype observed in hearts from p62-deficient mice may be due to p62-dependent mechanisms responsible for proteasomal dysfunction and apoptosis activation.

Sibling Death and Adult Maladjustment Indices: A Brief Report

ABSTRACTWhile symptoms of grief pose the most immediate psychological concern in the aftermath of sibling death, emerging research suggests that distal correlates may include strained interpersonal relations and externalized forms of psychological distress. College students with a history of Sibling Loss (n = 36), Parental Loss (n = 32), or No Loss (n = 367) were compared on the Minnesota Multiphasic Personality Inventory (MMPI-2). Sibling Loss was associated with higher Psychopathic Deviate (Pd; d = .62) and Hypomania (d = .42) scores. The relative risk (RR = 2.96) of a Pd elevation (T > 65) was higher after sibling death.