Age-stratified Model Research Articles

COVID-19 Global Mortality: Comparing Actual and Modelled Patterns in Space and Time Using an Infection Fatality Rate (IFR) Model

Background: International variations in COVID-19 mortality are stark and incompletely explained by age. We examined the global impact on COVID-19 mortality, including the proportion hypothetically infected, using an infection fatality rate (IFR) model.Methods: The age stratified IFR model was based on the distribution in UK and Diamond Princess cruise ship mortality data. We applied this model to more than 60 countries, comprising 86% of global population, using their age structure (from Population Pyramid) to estimate their expected average IFR. We used this IFR and reported mortality from Worldometer to estimate the hypothetical proportions of the population infected. We plotted the observed mortality monthly since March, examining countries by region of the world. We compared the hypothetical proportions infected with national sero-prevalence data.Results: Internationally, the average IFRs ranged from 40%, to generate the reported mortality. These hypothesised proportions were mostly higher than reported sero-prevalence.Interpretation: The model and graphic output help describe the pandemic and generate hypotheses for the observed differences. Mortality variations remaining unexplained by age could reflect differences in the: accuracy of data, proportion of the population infected, efficacy of public health interventions or pre-existing population resistance or vulnerability to infection. Funding: There was no external funding.Declaration of Interests: None.Ethics Approval Statement: No approvals were sought as all data were in the public domain.

Characterizing key attributes of COVID-19 transmission dynamics in China's original outbreak: Model-based estimations

A novel coronavirus strain, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. This study aims to characterize key attributes of SARS-CoV-2 epidemiology as the infection emerged in China. An age-stratified mathematical model was constructed to describe transmission dynamics and estimate age-specific differences in biological susceptibility to infection, age-assortativeness in transmission mixing, and transition in rate of infectious contacts (and reproduction number R0) following introduction of mass interventions. The model estimated the infectious contact rate in early epidemic at 0.59 contacts/day (95% uncertainty interval-UI = 0.48–0.71). Relative to those 60–69 years, susceptibility was 0.06 in those ≤19 years, 0.34 in 20–29 years, 0.57 in 30–39 years, 0.69 in 40–49 years, 0.79 in 50–59 years, 0.94 in 70–79 years, and 0.88 in ≥80 years. Assortativeness in transmission mixing by age was limited at 0.004 (95% UI = 0.002–0.008). R0 rapidly declined from 2.1 (95% UI = 1.8–2.4) to 0.06 (95% UI = 0.05–0.07) following interventions' onset. Age appears to be a principal factor in explaining the transmission patterns in China. The biological susceptibility to infection seems limited among children but high among those >50 years. There was no evidence for differential contact mixing by age.

Progress towards elimination of mother-to-child transmission of hepatitisB virus infection in China: a modelling analysis.

To determine the projected burden of hepatitisB virus (HBV) in China, the intervention strategies that can eliminate mother-to-child transmission (MTCT) by 2030 or earlier and the measurable parameters that can be used to monitor progress towards this target. We developed a dynamic, sex- and age-stratified model of the HBV epidemic in China, calibrated using hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) prevalence data from sequential national serosurveys (1979-2014) and the numbers of HBV-related cancer deaths (2012). We determined whether China can achieve elimination of MTCT of HBV by 2030 under current prevention interventions. We modelled various intervention scenarios to represent different coverage levels of birth-dose HBV vaccination, hepatitisB immunoglobulin to newborns of HBsAg-positive mothers and antiviral therapy (tenofovir) to HBeAg-positive pregnant women. We project that, if current levels of prevention interventions are maintained, China will achieve the elimination target by 2029. By modelling various intervention scenarios, we found that this can be brought forward to 2025 by increasing coverage of birth-dose vaccination, or to 2024 by the administration of tenofovir to HBeAg-positive pregnant women. We found that achievement of the target by 2025 would be predicted by a measurement of less than 2% MTCT in 2020. Our results highlight how high-quality national data can be combined with modelling in monitoring the elimination of MTCT of HBV. By demonstrating the impact of increased interventions on target achievement dates, we anticipate that other high-burden countries will be motivated to strengthen HBV prevention policies.

Burden of Congenital Rubella Syndrome (CRS) in Bangladesh: Systematic Review of Existing Literature and Transmission Modelling of Seroprevalence Studies.

Congenital Rubella Syndrome (CRS) is the leading cause of vaccine-preventable congenital anomalies. Comprehensive country-level data on the burden of CRS in low and middle-income countries, such as Bangladesh, are scarce. This information is essential for assessing the impact of rubella vaccination programs. We aim to systematically review the literature on the epidemiology of CRS and estimate the burden of CRS in Bangladesh. We conducted a systematic review of existing literature and transmission modelling of seroprevalence studies to estimate the pre-vaccine period burden of CRS in Bangladesh. OVID Medline (1948 - 23 November 2016) and OVID EMBASE (1974 - 23 November 2016) were searched using a combination of the database-specific controlled vocabulary and free text terms. We used an age-stratified deterministic model to estimate the pre-vaccination burden of CRS in Bangladesh. Ten articles were identified, published between 2000 and 2014, including seven crosssectional studies, two case series and one analytical case-control study. Rubella seropositivity ranged from 47.0% to 86.0% among all age population. Rubella sero-positivity increased with age. Rubella seropositivity among women of childbearing age was 81.0% overall. The estimated incidence of CRS was 0·99 per 1,000 live births, which corresponds to approximately 3,292 CRS cases annually in Bangladesh. The estimated burden of CRS in Bangladesh during the pre-vaccination period was high. This will provide important baseline information to assess the impact and cost-effectiveness of routine rubella immunisation, introduced in 2012 in Bangladesh.

0847 Association Between Cannabis Use Frequency and Sleep Duration Among a Representative Sample of US Adults

Abstract Introduction Cannabis use is on the rise in the US, and while the cannabis plant and related compounds are considered to have low toxicity, the impact on physiology including sleep remains unclear. Further, the bulk of cannabis research has focused on adolescents and young adults despite growing use among the elderly. Thus, this analysis sought to determine the impact of the frequency of cannabis use on sleep duration and determine if this relationship varies by age. Methods This cross-sectional study used data from the 2016-2018 Behavioral Risk Factor Surveillance System surveys. Multinomial logistic regression was used to evaluate the association between the frequency of cannabis use, 0-30 times over the prior 30 days; and average sleep duration, short (<7 hours); recommended (7-9 hours); and long (>9 hours) sleep. Results The study sample included 235,667 participants (48% male, 43% 18-44 years old and 35% 44-64 years old) of which 14,122 consumed cannabis. The weighted proportion who reported using cannabis 1-4x, 5-15x, or more than 16x/month were 3.1% (95% CI, 3.0%-3.3%), 2.1% (2.0%-2.2%), and 4.4% (4.2%-4.6%) respectively. In an age stratified model adjusted for sociodemographic and clinical characteristics, there were no associations between sleep and cannabis use up to 15x/month. Among those adults who consumed cannabis more than 16x/month: (1) 18-44 year olds were more likely to report either short sleep (risk ratio (RR), 1.21; 95% CI, 1.05-1.39) or long sleep (RR, 1.57; 95% CI, 1.11-2.22) as opposed to the recommended amount of sleep; whereas (2) 44-64 year olds demonstrated an increased risk for long sleep (RR, 1.77; 95% CI, 1.09-2.89); and (3) participants 65 years and older demonstrated an increased risk for short sleep (RR, 1.61; 95% CI, 1.04-2.49). Conclusion We demonstrate that modest cannabis use was not associated with sleep, whereas daily cannabis use is associated with age-dependent sleep duration above and below the recommended amount. Support KL2TR002370, 2R25HL105444-09.

Influence of demographically-realistic mortality schedules on vaccination strategies in age-structured models

Because demographic realism complicates analysis, mathematical modelers either ignore demography or make simplifying assumptions (e.g., births and deaths equal). But human populations differ demographically, perhaps most notably in their mortality schedules. We developed an age-stratified population model with births, deaths, aging and mixing between age groups. The model includes types I and II mortality as special cases. We used the gradient approach (Feng et al., 2015, 2017) to explore the impact of mortality patterns on optimal strategies for mitigating vaccine-preventable diseases such as measles and rubella, which the international community has targeted for eradication. Identification of optimal vaccine allocations to reduce the effective reproduction number Rv under various scenarios is presented. Numerical simulations of the model with various types of mortality are carried out to ascertain the long-term effects of vaccination on disease incidence. We conclude that both optimal vaccination strategies and long-term effects of vaccination may depend on demographic assumptions.

Public health and economic impact of switching from a trivalent to a quadrivalent inactivated influenza vaccine in Mexico

ABSTRACT Most influenza vaccines in Mexico are trivalent, containing two influenza A strains and a single B strain. Quadrivalent influenza vaccines (QIVs) extend protection by including an additional B strain to cover both co-circulating B lineages. Here, we retrospectively estimated how a switch to QIV in Mexico would have impacted influenza-related health outcomes over the 2010/2011 to 2015/2016 influenza seasons, and prospectively estimated the budget impact of using QIV in Mexico’s national immunization program from 2016/2017 to 2020/2021. For the retrospective estimation, we used an age-stratified static model incorporating Mexico-specific input parameters. For the prospective estimation, we used a budget impact model based on retrospective attack rates considering predicted future vaccination coverage. Between 2010/2011 and 2015/2016, a switch to QIV would have prevented 270,596 additional influenza cases, 102,000 general practitioner consultations, 140,062 days of absenteeism, 3,323 hospitalizations, and 312 deaths, saving Mex$214 million (US$10.8 million) in third-party payer costs. In the prospective analysis, a switch to QIV was estimated to prevent an additional 225,497 influenza cases, 85,000 general practitioner consultations, 116,718 days of absenteeism, 2,769 hospitalizations, and 260 deaths, saving Mex$178 million (US$9 million) in third-party payer costs over 5 years. Compared to the trivalent vaccine, the benefit and costs saved with QIV were sensitive to the distribution of influenza A vs. B cases and trivalent vaccine effectiveness against the mismatched B strain. These results suggest switching to QIV in Mexico would benefit healthcare providers and society by preventing influenza cases, morbidity, and deaths, and reducing associated use of medical resources.

Are social inequalities in influenza vaccination coverage in Japan reduced by health policy?

Influenza vaccination is effective to prevent influenza infection. However, findings about association between socioeconomic status and influenza vaccination coverage are controversial. Online survey was conducted among 4995 participants between 20 and 69 years of age throughout Japan, January 2017. We asked about history of receiving vaccination in previous year and socioeconomic status, with their reasons for having vaccination or not. Age stratified multivariable logistic regression model was conducted to estimate the odds ratio (ORs) and 95% confidence intervals (CIs) of receiving vaccine for each educational level and income. Sex, self-reported health status, marital status and income were included as covariates. The rate for receiving influenza vaccine among ≤64 year-olds and ≥65 year-olds was 32.9% and 35.4%, respectively. Among younger adults, vaccination varied by each education: junior high school, 23.6%; senior high school, 27.2%; college, 32.6%; university, 36.2%; and graduate school, 39.8%. Compared to junior high school, those from graduate school tended to be more vaccinated (OR1.88, 95%CI 1.07–3.24). On the contrary, those aged above ≥65 years old received vaccination with no significant differences across education. Likewise, among respondents aged ≤64 year-olds, income was significantly associated with influenza vaccination. Despite being “Managed by school or company” (32.5%), having “No particular reason” was the frequent reason for both receiving influenza vaccination (23.8%) or not (34.3%). Adults with higher educational level were significantly more likely to receive vaccination. Subsidizing influenza vaccination may reduce inequality in receiving vaccination for adults. Strengthening vaccination through various approaches is necessary, such as managing by school or company.

Prospective evaluation of a clinical decision tool to reduce childhood admissions to PICUs for poisoning: ReCAP2

Aim: To prospectively validate a pediatric clinical prediction model to identify children at low risk of clinically significant ingestions to prevent unnecessary pediatric intensive care unit (PICU) admissions.Methods: Calls received by the Georgia Poison Center about children for acute ingestions between May 25, 2017 and May 17, 2018 were scored in real time using the full, age-stratified, and simplified clinical scoring tool to reduce childhood admissions to PICUs for poisoning (RECAP2). Clinically significant ingestions with a poison center recommendation of PICU admission are defined in the simple RECAP2 model as ingestion of clonidine, ethanol, an oral anti-hyperglycemic agent, or exposure to carbon monoxide, as well as the presence of symptoms occurring within 2 h for an immediate release, or 4 h for an extended release, medication exposure. Model statistics and percent reduction in PICU admissions were computed.Results: There were 886 children admitted after ingestions, of which 454 (51.2%) children were admitted to intensive care. At the time of the initial poison center call to report the ingestion, 44 cases (5%) were incomplete using the full, age-stratified model compared to the complete scoring using the simple scoring model. Seventy-two children (8.1%) required monitoring or interventions performed only in a PICU. Real-time application of the full model compared with the simple model would have reduced PICU admissions by 33.3 and 31.7%, respectively.Conclusions: The simple RECAP2 clinical scoring model is a sensitive prediction tool to identify children at very low risk for clinically significant ingestions for whom PICU admission can be avoided. Clinical implementation of the simple RECAP2 model and recommendation for admission to an inpatient unit versus PICU should be further evaluated, to reduce unnecessary PICU admissions following acute ingestions.

Development of a resource allocation formula for substance misuse treatment services

Funding for substance misuse services comprises one-third of Public Health spend in England. The current allocation formula contains adjustments for actual activity, performance and need, proxied by the Standardized Mortality Ratio for under-75s (SMR < 75). Additional measures, such as deprivation, may better identify differential service need. We developed an age-standardized and an age-stratified model (over-18s, under-18s), with the outcome of expected/actual cost at postal sector/Local Authority level. A third, person-based model incorporated predictors of costs at the individual level. Each model incorporated both needs and supply variables, with the relative effects of their inclusion assessed. Mean estimated annual cost (2013/14) per English Local Authority area was £5 032 802 (sd: 3 951 158). Costs for drug misuse treatment represented the majority (83%) of costs. Models achieved adjusted R-squared values of 0.522 (age-standardized), 0.533 (age-stratified over-18s), 0.232 (age-stratified under-18s) and 0.470 (person-based). Improvements can be made to the existing resource allocation formulae to better reflect population need. The person-based model permits inclusion of a range of needs variables, in addition to strong predictors of cost based on the receipt of treatment in the previous year. Adoption of this revised person-based formula for substance misuse would shift resources towards more deprived areas.

Variation in loss of immunity shapes influenza epidemics and the impact of vaccination

BackgroundProtective antibody immunity against the influenza A virus wanes in 2–7 years due to antigenic drift of the virus’ surface proteins. The duration of immune protection is highly variable because antigenic evolution of the virus is irregular. Currently, the variable nature of the duration of immunity has had little attention in analyses of the impact of vaccination, including cost-effectiveness studies.MethodsWe developed a range of mathematical transmission models to investigate the effect of variable duration of immunity on the size of seasonal epidemics. The models range from simple conceptual to more realistic, by distinguishing between infection- versus vaccination-induced immunity, by inclusion of primary vaccine failure, by assuming a leaky vaccine, and by the inclusion of age-dependent contact patterns.ResultsWe show that annual variation in the duration of immunity causes large variation in the size of epidemics, and affects the effectiveness of vaccination. Accumulation of susceptible individuals in one or more mild seasons results in a disproportionately large outbreak in a subsequent season. Importantly, variation in the duration of immunity increases the average infection attack rate when the vaccination coverage is around the outbreak threshold. Specifically, in a tailored age-stratified model with a realistic reproduction number (R0 = 1.4) and vaccination coverage of 25%, we find that the attack rate in unvaccinated children (<10 years old) is negligible if the duration of immunity is constant, while on average 2.8% (2.5–97.5% percentiles: 1.8–4.1%) of the children are infected if the duration of immunity is variable. These findings stem from the buildup of susceptibility over multiple seasons by waning of immunity, and the nonlinear relation between susceptibility and infection attack rates.ConclusionsThe models illustrate that variation in the duration of immunity impacts the long-term effectiveness of vaccination, and that vaccine effectiveness cannot be judged for each year in isolation. Our findings have implications for vaccination strategies that aim to maximize the vaccination coverage while extending the age range of persons eligible for vaccination.

Changing Dynamics of HIV Transmission in Côte d'Ivoire: Modeling Who Acquired and Transmitted Infections and Estimating the Impact of Past HIV Interventions (1976–2015)

Understanding the impact of past interventions and how it affected transmission dynamics is key to guiding prevention efforts. We estimated the population-level impact of condom, antiretroviral therapy (ART), and prevention of mother-to-child transmission activities on HIV transmission and the contribution of key risk factors on HIV acquisition and transmission. An age-stratified dynamical model of sexual and vertical HIV transmission among the general population, female sex workers (FSW), and men who have sex with men was calibrated to detailed prevalence and intervention data. We estimated the fraction of HIV infections averted by the interventions, and the fraction of incident infections acquired and transmitted by different populations over successive 10-year periods (1976-2015). Overall, condom use averted 61% (95% credible intervals: 56%-66%) of all adult infections during 1987-2015 mainly because of increased use by FSW (46% of infections averted). In comparison, ART prevented 15% (10%-19%) of adult infections during 2010-2015. As a result, FSW initially (1976-1985) contributed 95% (91%-97%) of all new infections, declining to 19% (11%-27%) during 2005-2015. Older men and clients mixing with non-FSW are currently the highest contributors to transmission. Men who have sex with men contributed ≤4% transmissions throughout. Young women (15-24 years; excluding FSW) do not transmit more infections than they acquired. Early increases in condom use, mainly by FSW, have substantially reduced HIV transmission. Clients of FSWs and older men have become the main source of transmission, whereas young women remain at increased risk. Strengthening prevention and scaling-up of ART, particularly to FSW and clients of female sex workers, is important.

Population-level impact of an accelerated HIV response plan to reach the UNAIDS 90-90-90 target in Côte d'Ivoire: Insights from mathematical modeling.

BackgroundNational responses will need to be markedly accelerated to achieve the ambitious target of the Joint United Nations Programme on HIV/AIDS (UNAIDS). This target aims for 90% of HIV-positive individuals to be aware of their status, for 90% of those aware to receive antiretroviral therapy (ART), and for 90% of those on treatment to have a suppressed viral load by 2020, with each individual target reaching 95% by 2030. We aimed to estimate the impact of various treatment-as-prevention scenarios in Côte d’Ivoire, one of the countries with the highest HIV incidence in West Africa, with unmet HIV prevention and treatment needs, and where key populations are important to the broader HIV epidemic.Methods and findingsAn age-stratified dynamic model was developed and calibrated to epidemiological and programmatic data using a Bayesian framework. The model represents sexual and vertical HIV transmission in the general population, female sex workers (FSW), and men who have sex with men (MSM). We estimated the impact of scaling up interventions to reach the UNAIDS targets, as well as the impact of 8 other scenarios, on HIV transmission in adults and children, compared to our baseline scenario that maintains 2015 rates of testing, ART initiation, ART discontinuation, treatment failure, and levels of condom use. In 2015, we estimated that 52% (95% credible intervals: 46%–58%) of HIV-positive individuals were aware of their status, 72% (57%–82%) of those aware were on ART, and 77% (74%–79%) of those on ART were virologically suppressed. Reaching the UNAIDS targets on time would avert 50% (42%–60%) of new HIV infections over 2015–2030 compared to 30% (25%–36%) if the 90-90-90 target is reached in 2025. Attaining the UNAIDS targets in FSW, their clients, and MSM (but not in the rest of the population) would avert a similar fraction of new infections (30%; 21%–39%). A 25-percentage-point drop in condom use from the 2015 levels among FSW and MSM would reduce the impact of reaching the UNAIDS targets, with 38% (26%–51%) of infections averted. The study’s main limitation is that homogenous spatial coverage of interventions was assumed, and future lines of inquiry should examine how geographical prioritization could affect HIV transmission.ConclusionsMaximizing the impact of the UNAIDS targets will require rapid scale-up of interventions, particularly testing, ART initiation, and limiting ART discontinuation. Reaching clients of FSW, as well as key populations, can efficiently reduce transmission. Sustaining the high condom-use levels among key populations should remain an important prevention pillar.

Counting the cost of cancer: out-of-pocket payments made by colorectal cancer survivors.

Cancer places a significant cost burden on health services. There is increasing recognition that cancer also imposes a financial and economic burden on patients but this has rarely been quantified outside North America. We investigate out-of-pocket costs (OOPCs) incurred by colorectal (CRC) survivors in Ireland. CRC survivors (ICD10 C18-20) diagnosed 6-30months previously were identified from the National Cancer Registry Ireland and invited to complete a postal questionnaire. Cancer-related OOPC for tests, procedures, drugs, allied medications and household management in approximately the year following diagnosis were calculated. Robust regression was used to identify predictors of OOPC; this was done for all survivors combined and stratified by age (<70 and ≥70years) and employment status (working and not working) at diagnosis. Four hundred ninety-seven CRC survivors completed questionnaires (response rate=39%). Almost all (90%) respondents reported some cancer-related OOPC. The average total OOPC was €1589. Stage III at diagnosis was associated with significantly higher OOPCs than other stages in the all-survivor model, in those not working in the employment model and in those under 70years in the age-stratified model. In all-survivor model, those under 70 also had higher OOPCs, as did those in employment. Having one or more children was associated with significantly lower OOPCs in those under 70years. Almost all CRC survivors incur cancer-related OOPCs; for some, these are not insignificant. Greater attention should be paid to the development of services to help survivors manage the financial and economic burden of cancer.

Cost-Effectiveness of Pertussis Vaccination During Pregnancy in the United States.

Vaccination against pertussis has reduced the disease burden dramatically, but the most severe cases and almost all fatalities occur in infants too young to be vaccinated. Recent epidemiologic evidence suggests that targeted vaccination of mothers during pregnancy can reduce pertussis incidence in their infants. To evaluate the cost-effectiveness of antepartum maternal vaccination in the United States, we created an age-stratified transmission model, incorporating empirical data on US contact patterns and explicitly modeling parent-infant exposure. Antepartum maternal vaccination incurs costs of $114,000 (95% prediction interval: 82,000, 183,000) per quality-adjusted life-year, in comparison with the strategy of no adult vaccination, and is cost-effective in the United States according to World Health Organization criteria. By contrast, vaccinating a second parent is not cost-effective, and vaccination of either parent postpartum is strongly dominated by antepartum maternal vaccination. Nonetheless, postpartum vaccination of mothers who were not vaccinated antepartum improves upon the current recommendation of untargeted adult vaccination. Additionally, the temporary direct protection of the infant due to maternal antibody transfer has efficacy for infants comparable to that conferred to toddlers by the full primary vaccination series. Efficient protection against pertussis for infants begins before birth. We highly recommend antepartum vaccination for as many US mothers as possible.

Abstract 5589: Age-stratified risk of unexpected uterine sarcoma following surgery for presumed benign leiomyoma

Abstract Background: Estimates of unexpected uterine sarcoma following surgery for presumed benign leiomyoma that utilize age-stratification are lacking. Patients and Methods: A retrospective cohort of 2075 patients that had undergone myomectomy was evaluated to determine the case incidence of unexpected uterine sarcoma. An aggregate risk estimate was generated using a meta-analysis of similar studies plus our cohort. Database-derived age distributions of the incidence rates of uterine sarcoma and uterine leiomyoma surgery were used to stratify risk by age. Results: Of 2075 patients in our cohort, six were diagnosed with uterine sarcoma. Our meta-analysis revealed 8 studies from 1980-2014. Combined with our cohort, there are 18 cases of leiomyosarcoma reported in 10120 patients, for an aggregate risk of 1.78 per 1000 [95% CI: 1.1-2.8], or 1 in 562. There are 8 cases of other uterine sarcomas reported in 6889 patients, for an aggregate risk of 1.16 per 1000 [95% CI: 0.5-4.9], or 1 in 861. The summation of these risks gives an overall risk of uterine sarcoma of 2.94 per 1000 [95% CI: 1.8-4.1], or 1 in 340. After stratification by age, we predict the risk of uterine sarcoma to range from a peak of 10.1 cases per 1000, or 1 in 98, for age 75-79 to less than 1 case per 500 for age &amp;lt;30. Conclusion: The risk of unexpected uterine sarcoma varies significantly across age groups. Our age-stratified predictive model should be incorporated to more accurately counsel patients and to assist in providing guidelines for surgical technique for leiomyoma. Age-stratified risk of unexpected uterine sarcoma at the time of surgery for presumed leiomyomaAgeEstimated(years)Risk of Uterine Sarcoma (per 1000 procedures)25-291.74(1 in 574)30-342.01(1 in 496)35-392.65(1 in 377)40-442.46(1 in 405)45-493.28(1 in 304)50-544.62(1 in 216)55-596.35(1 in 158)60-646.36(1 in 157)65-697.53(1 in 133)70-748.55(1 in 117)75-7910.1(1 in 98)80-845.57(1 in 179) Citation Format: Andrew S. Brohl, Li Li, Vaagn Andikyan, Angela Cioffi, Joel T. Dudley, Andrew Kasarskis, Robert G. Maki. Age-stratified risk of unexpected uterine sarcoma following surgery for presumed benign leiomyoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5589. doi:10.1158/1538-7445.AM2015-5589

Age-stratified risk of unexpected uterine sarcoma following surgery for presumed benign leiomyoma.

Estimates of unexpected uterine sarcoma following surgery for presumed benign leiomyoma that use age-stratification are lacking. A retrospective cohort of 2,075 patients that had undergone myomectomy was evaluated to determine the case incidence of unexpected uterine sarcoma. An aggregate risk estimate was generated using a meta-analysis of similar studies plus our data. Database-derived age distributions of the incidence rates of uterine sarcoma and uterine leiomyoma surgery were used to stratify risk by age. Of 2,075 patients in our retrospective cohort, 6 were diagnosed with uterine sarcoma. Our meta-analysis revealed 8 studies from 1980 to 2014. Combined with our study, 18 cases of leiomyosarcoma are reported in 10,120 patients, for an aggregate risk of 1.78 per 1,000 (95% confidence interval [CI]: 1.1-2.8) or 1 in 562. Eight cases of other uterine sarcomas were reported in 6,889 patients, for an aggregate risk of 1.16 per 1,000 (95% CI: 0.5-4.9) or 1 in 861. The summation of these risks gives an overall risk of uterine sarcoma of 2.94 per 1,000 (95% CI: 1.8-4.1) or 1 in 340. After stratification by age, we predict the risk of uterine sarcoma to range from a peak of 10.1 cases per 1,000, or 1 in 98, for patients aged 75-79 years to <1 case per 500 for patients aged <30 years. The risk of unexpected uterine sarcoma varies significantly across age groups. Our age-stratified predictive model should be incorporated to more accurately counsel patients and to assist in providing guidelines for the surgical technique for leiomyoma.

Combating pertussis resurgence: One booster vaccination schedule does not fit all

Pertussis has reemerged as a major public health concern in many countries where it was once considered well controlled. Although the mechanisms responsible for continued pertussis circulation and resurgence remain elusive and contentious, many countries have nevertheless recommended booster vaccinations, the timing and number of which vary widely. Here, using a stochastic, age-stratified transmission model, we searched for cost-effective booster vaccination strategies using a genetic algorithm. We did so assuming four hypothesized mechanisms underpinning contemporary pertussis epidemiology: (I) insufficient coverage, (II) frequent primary vaccine failure, (III) waning of vaccine-derived protection, and (IV) vaccine "leakiness." For scenarios I-IV, successful booster strategies were identified and varied considerably by mechanism. Especially notable is the inability of booster schedules to alleviate resurgence when vaccines are leaky. Critically, our findings argue that the ultimate effectiveness of vaccine booster schedules will likely depend on correctly pinpointing the causes of resurgence, with misdiagnosis of the problem epidemiologically ineffective and economically costly.

Predictive Utility of Type and Duration of Symptoms at Initial Presentation in Patients with Mild Cognitive Impairment

Background/Aims: To assess (1) the duration and symptoms present in participants with mild cognitive impairment (MCI) and (2) the impact of these variables on predicting conversion to Alzheimer’s disease (AD). Methods: Participants with MCI (n = 148) were assessed and followed systematically. Results: Decline in memory was reported as the first symptom in 118 of the cases. Converters had more symptoms (e.g. language decline, depression), and the combination of decline in memory and in performance of high-order social/cognitive activities as well as disorientation more often than nonconverters (p = 0.036). In an age-stratified Cox model, predictors of conversion to AD were shorter time since onset of memory decline and lower baseline MMSE score. Conclusions: Recent onset of memory decline with older age, decreased MMSE score, change in performance and disorientation indicate a greater likelihood of short-term conversion to AD.

Improving the Imputation of Race: Evaluating the Benefits of Stratifying by Age

Health plans and other health care institutions may use indirect methods such as geocoding and surname analysis to estimate race, ethnicity, and socioeconomic status in an effort to measure disparities in care or target specific demographics. This study investigated whether stratifying by age improved imputations of race and ethnicity made through geocoding. Self-reported race and ethnicity from Medicaid enrollment records and from a health risk assessment administered by a large employer were used to validate imputation results from both an age-stratified model and a standard model. Sensitivity, specificity, and positive predictive value were calculated. Both approaches successfully imputed race and ethnicity for whites, blacks, Asians, and Hispanics. The age-stratified approach identified more blacks than did the unstratified approach, and correctly identified more blacks and whites. The two approaches worked equally well for identifying Asians and Hispanics. Age stratification may improve the accuracy of imputation methods, and help health care organizations to better understand the demographics of the people they serve.