Population-level Outcomes Research Articles

Trends of extreme hyperbilirubinemia related infant mortality in select European countries (1990-2019).

Limited data exist on population-level mortality outcomes related to extreme neonatal hyperbilirubinemia (EHB) and this study examines trends in annual infant mortality rate (IMR) attributed to hemolytic and perinatal jaundice among Germany, France, Italy, Portugal, Greece and Spain from 1990 to 2019. Data on annual incident cases and disability-adjusted life years were collected from the 2019 Global Burden of Disease study. Live birth cohort data were sourced from UN World Population Prospects. We quantified temporal trends, with relative percent changes. Average annual percent changes (AAPCs) were evaluated using the Joinpoint Regression Program. EHB-related infant mortality decreased from 21.4 (95%CI: 16.1, 27.1) in 1990 to 4.2 (95%CI: 1.9, 7.6) per million live births in 2019. Germany demonstrated lowest AAPC of -3.2% (95% CI: -3.8, -2.5), while Portugal had the highest AAPC of -8.6% (95% CI -11.9, -5.1) in reducing infant mortality due to EHB. There were distinct divergences in the trajectories of declining EHB mortality among the studied countries. This study highlights a significant decline in infant mortality due to extreme hyperbilirubinemia, emphasizing the need for national surveillance and tailored guidelines to prevent bilirubin induced neurological damage. This cross-sectional analysis revealed a marked decline in infant mortality rates attributed to extreme hyperbilirubinemia across the selected European countries. The rates of decline varied significantly between countries, demonstrating notable heterogeneity in mortality trends when stratified by age at death. Implementing data-driven surveillance systems can optimize the alignment of equitable healthcare services, strengthen accountability measures, and identify critical operational inefficiencies. In the European Union, country-specific hyperbilirubinemia guidelines should be reinforced to ensure effective screening and post-discharge follow-up protocols that are tailored to risk burden and available healthcare resources.

An Adverse Outcome Pathway Approach Linking Retinoid Signaling Disruption to Teratogenicity and Population-Level Outcomes

Recent research efforts in endocrine disruption have focused on evaluating non-EATS (estrogen, androgen, thyroid, and steroidogenesis) pathways. Retinoid signaling disruption is noteworthy because of its teratogenic effects and environmental relevance. However, current environmental risk assessments are limited in their ability to evaluate impacts on individuals and populations. This study characterizes an Adverse Outcome Pathway (AOP) network linking retinoid signaling disruption to teratogenicity and survival in zebrafish. We identified Retinoic Acid Receptor (RAR) overactivation as the molecular initiating event leading to key events including craniofacial (CFM) and tail (TM) malformations, posterior swim bladder (SB) non-inflation, impaired swimming performance, and reduced feeding, ultimately resulting in decreased survival. Our study (1) determines critical sensitivity windows for CFM, posterior SB non-inflation, and TM, (2) provides quantitative measurements for CFM and TM, and (3) defines impacts on higher biological levels including food ingestion, swimming, and survival. Results show that all-trans retinoic acid (ATRA) induces strong teratogenic effects with sensitivity windows between 4-48 hours post fertilization (hpf) for CFM, TM, and posterior SB non-inflation. TM is the most sensitive indicator, with EC50 of 0.2 - 0.26 µg/L across exposure windows 4-48, 4-72, 4-96, and 4-120 hpf. Besides inducing known malformations, ATRA impaired posterior SB inflation with EC50 of 1 - 1.21 µg/L across the same exposure windows. ATRA exposure (1 µg/L) resulted in 50% food ingestion inhibition at 7 days post fertilization (dpf) and 10% survival at 14 dpf. This study provides a regulatory-relevant framework linking developmental effects to population outcomes, highlighting ecological risks and needs for improved risk assessments.

Functional Traits Predict Outcomes of Current and Novel Competition Under Warmer Climate.

Functional traits offer a potential avenue to generalize and forecast the impacts of changing competition on plant communities, including changing outcomes of competition among species that currently interact (current competition) or that will interact in the future following range shifts (novel competition). However, it remains unclear how well traits explain variation in the outcomes of current and novel competition as well as the underlying processes determining coexistence or competitive exclusion, under changing climate. Here, we interacted pairs of high and low-elevation species in three sites across an elevation gradient in the Swiss Alps. For each species pair, we quantified the population-level outcomes of competition (invasion growth rates), relative fitness differences, and niche overlap and related these to 15 functional traits that were measured in each site. Most traits were significantly associated with invasion growth rates at the low elevation, where species had greater relative fitness differences, but these associations were much weaker towards higher elevations. This appears to be because traits, particularly those associated with light competition, captured species' relative fitness differences at lower elevations, but not at the high elevation site, highlighting that the predictive ability of traits can depend on environmental context. The amplified relative fitness differences towards lower elevations suggest that climate warming may increase the likelihood of competitive exclusion. In addition, novel competitors tended to show greater niche overlap than current competitors, leading to stronger overall competitive effects. However, in general, trait differences predicted competitive outcomes of novel and current competitors similarly well, suggesting that traits can predict interactions between species that do not yet interact. Our study reinforces the importance of considering changing interactions for predicting species responses to climate change and provides experimental evidence supporting the usefulness of functional trait differences in forecasting the impacts of future plant interactions under changing climate.

Days at Home After Traumatic Brain Injury: Moving Beyond Mortality to Evaluate Patient-Centered Outcomes Using Population Health Data.

Administrative data are invaluable for assessing outcomes at the population level. However, there are few validated patient-centered outcome measures that capture morbidity following traumatic brain injury (TBI) using these data. We sought to characterize and validate days at home (DAH) as a measure to quantify population-level outcomes after moderate to severe TBI. We additionally assessed the earliest feasible outcome assessment period for patients with TBI using this outcome measure. This multicenter retrospective cohort study used linked health administrative data sources to identify adults with moderate to severe TBI presenting to trauma centers in Ontario, Canada, between 2009 and 2021. DAH at 180 days (DAH180 days) reflects the total number of days spent alive and at home excluding the days spent institutionalized across care settings. Construct validity was determined using hierarchical quantile regression to assess the associations between clinical and injury covariates with DAH180 days. Predictive validity was assessed using Spearman rank correlation. We estimated minimally important difference (MID) in DAH180 days to aid with outcome measure interpretability. There were 6,340 patients who met inclusion criteria. Median DAH180 days was 70 days (interquartile range 0-144). Mortality occurred in 2,162 (34.1%) patients within 90 days following injury. Patients in the lower DAH180 days group were more commonly older (absolute standardized difference [ASD] = 0.68) with higher preinjury health resource utilization (ASD = 0.36) and greater injury severity (ASD = 0.81). Increased baseline health resource utilization (-10.1 days, 95% CI -17.4 to -2.8, p = 0.0041), older age (-4.6 days, 95% CI -5.7 to -3.4, p < 0.001), higher cranial injury severity (-84.6 days, 95% CI -98.3 to -71.0, p < 0.001), and major extracranial injuries (-14.2 days, 95% CI -19.5 to -8.93, p < 0.001) were significantly associated with fewer DAH180 days. DAH180 days was positively correlated with DAH at up to 3 years (r = 0.91, 95% CI 0.90-0.92) and negatively correlated with direct health care expenditure (rs = -0.89, 95% CI -0.88 to -0.90). The average MID estimated from anchor-based and distribution-based methods was 18 days. We validate DAH180 days as a potentially useful outcome measure with construct, predictive, and face validity in a population with moderate to severe TBI. Given the intensity of acute care requirements for patients with TBI, our work highlights DAH180 days as a feasible and sufficiently responsive outcome measure.

Association of Racial Residential Segregation and Other Social Determinants of Health with HIV Late Presentation.

Understanding social determinants of HIV late presentation with advanced disease (LPWA) beyond individual-level factors could help decrease LPWA and improve population-level HIV outcomes. This study aimed to examine county-level social determinants of health (SDOH) with HIV late presentation. We aggregated datasets for analysis by linking statewide HIV diagnosis data from the South Carolina (SC) Enhanced HIV/AIDS Reporting System and multiple social contextual datasets (e.g., the American Community Survey). All adult (18 years and older) people with HIV diagnosed from 2014 to 2019 in SC were included. Linear mixed models with forward selection were employed to explore the association of county-level SDOH with the county-level three-year moving average percentage of LPWA and average delay time from HIV infection to diagnosis. Around 30% of new HIV diagnoses were LPWA in SC, and the mean delay time for people with LPWA was approximately 13 years. Counties with more racial residential segregation had longer average delay time (Adjusted beta = 5.079, 95% CI: 0.268 ~ 9.889). Regarding other SDOH, the increased percentage of LPWA was associated with fewer Ryan White centers per 100,000 population (Adjusted beta = -0.006, 95% CI: -0.011~-0.001) and higher percentages of the population with less than a high school education (Adjusted beta = 0.008, 95% CI: 0 ~ 0.015). Reducing county-level disparities in LPWA requires multifaceted interventions addressing multiple dimensions of SDOH. Targeted interventions are needed for counties with more Black residential segregation, fewer Ryan White centers, and higher percentages of less than high school education.

The Contribution of Hypertensive Disorders of Pregnancy to Neonatal Unit Admissions and Iatrogenic Preterm Delivery at < 34+0 Weeks' Gestation in the UK: A Population-Based Study Using the National Neonatal Research Database.

The objectives of this study were to (i) quantify the contribution of maternal hypertensive disorders of pregnancy (HDP) to iatrogenic preterm birth (PTB) and neonatal unit (NNU) admissions < 34+0 weeks and (ii) describe short-term population-level outcomes for HDP infants, exploring ethnic disparities and comparing outcomes by HDP exposure. Retrospective population-based study using the National Neonatal Research Database. England and Wales. Infants born < 34+0 weeks and admitted to NNU 2012-2020. Descriptive statistics, linear and logistic regression models to compare outcomes between groups. Survival to discharge with/without comorbidity. 122 228 infants met inclusion criteria. Where collected, 49 839/114 164 (43.7%, 95% CI 43.4%-43.9%) of infants had an iatrogenic PTB. HDP was recorded in 16 510/122 228 (13.5%) of all infants and 13 560/49 839 (27.2%) of iatrogenic PTBs. HDP and/or foetal growth restriction (FGR) were recorded in 24 124/49 839 (48.4%) of iatrogenic PTBs. Singleton HDP infants < 10th BWC had ≥ 90% survival to discharge from 28 weeks' gestation, versus from 26 weeks' gestation for those born ≥ 10th BWC. In extreme preterm HDP infants (< 27 weeks), 27.3% of infants < 10th BWC died compared to 15.2% of those ≥ 10th BWC. Survival without comorbidity was ≥ 90% from 32 weeks' gestation in HDP infants across BWC. These contemporaneous population-level data show that almost one in two PTB < 34+0 weeks' gestation are iatrogenic, with HDP and/or FGR being the major contributors to iatrogenic prematurity. This has substantial implications for strategies to reduce preterm birth in the UK and internationally. The data further inform antenatal and at-birth counselling of HDP-exposed infants.

Elective Induction of Labor May Have Negative Effects at the Hospital Level

Labor induction increased in the United States after the publication of A Randomized Trial of Induction Versus Expectant Management (ARRIVE) in 2018. During this trial, investigators found that elective induction at 39 weeks in low-risk nulliparous women led to similar perinatal outcomes when compared to expectant management. However, other researchers have since linked rising labor induction rates to worse hospital- and population-level outcomes. It is possible that elective induction of labor has a neutral effect on patients who are induced while at the same time lessening hospital capacity to care for other maternity patients, which leads to a negative effect on patient outcomes overall. During a trial, this represents a form of negative spillover, in which an intervention indirectly harms the comparison group and leads to overestimation of intervention benefit. Although further research is needed, evidence the ARRIVE and subsequent studies provides preliminary support for this possibility.

Smoke-free legislation impact on the hospitality sector in the Republic of Georgia

IntroductionComprehensive smoke-free (SF) policies reduce secondhand smoke exposure and improve population-level health outcomes. However, some decision-makers heed the tobacco industry’s argument that SF policies negatively impact the hospitality sector. This...

Collective Intelligence-Based Participatory COVID-19 Surveillance in Accra, Ghana: Pilot Mixed Methods Study.

Infectious disease surveillance is difficult in many low- and middle-income countries. Information market (IM)-based participatory surveillance is a crowdsourcing method that encourages individuals to actively report health symptoms and observed trends by trading web-based virtual "stocks" with payoffs tied to a future event. This study aims to assess the feasibility and acceptability of a tailored IM surveillance system to monitor population-level COVID-19 outcomes in Accra, Ghana. We designed and evaluated a prediction markets IM system from October to December 2021 using a mixed methods study approach. Health care workers and community volunteers aged ≥18 years living in Accra participated in the pilot trading. Participants received 10,000 virtual credits to trade on 12 questions on COVID-19-related outcomes. Payoffs were tied to the cost estimation of new and cumulative cases in the region (Greater Accra) and nationwide (Ghana) at specified future time points. Questions included the number of new COVID-19 cases, the number of people likely to get the COVID-19 vaccination, and the total number of COVID-19 cases in Ghana by the end of the year. Phone credits were awarded based on the tally of virtual credits left and the participant's percentile ranking. Data collected included age, occupation, and trading frequency. In-depth interviews explored the reasons and factors associated with participants' user journey experience, barriers to system use, and willingness to use IM systems in the future. Trading frequency was assessed using trend analysis, and ordinary least squares regression analysis was conducted to determine the factors associated with trading at least once. Of the 105 eligible participants invited, 21 (84%) traded at least once on the platform. Questions estimating the national-level number of COVID-19 cases received 13 to 19 trades, and obtaining COVID-19-related information mainly from television and radio was associated with less likelihood of trading (marginal effect: -0.184). Individuals aged <30 years traded 7.5 times more and earned GH ¢134.1 (US $11.7) more in rewards than those aged >30 years (marginal effect: 0.0135). Implementing the IM surveillance was feasible; all 21 participants who traded found using IM for COVID-19 surveillance acceptable. Active trading by friends with communal discussion and a strong onboarding process facilitated participation. The lack of bidirectional communication on social media and technical difficulties were key barriers. Using an IM system for disease surveillance is feasible and acceptable in Ghana. This approach shows promise as a cost-effective source of information on disease trends in low- and middle-income countries where surveillance is underdeveloped, but further studies are needed to optimize its use.

The population-level effects of omitting chemotherapy guided by a 21-gene expression assay in node-positive breast cancer: a simulation modeling study

BackgroundA recent trial showed that postmenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative, lymph node-positive (1–3 nodes) breast cancer with a 21-gene recurrence score of ≤ 25 could safely omit chemotherapy. However, there are limited data on population-level long-term outcomes associated with omitting chemotherapy among diverse women seen in real-world practice.MethodsWe adapted an established, validated simulation model to generate the joint distributions of population-level characteristics of women diagnosed with early-stage breast cancer in the U.S. Input parameters were derived from cancer registry, meta-analyses, and clinical trial data. The effects of omitting chemotherapy on 10-year distant recurrence-free survival, life-years, and quality adjusted life-years (QALYs) were modeled for premenopausal and postmenopausal women. QALYs were discounted at 3%. Results were evaluated for subgroups stratified by race and ethnicity. Sensitivity analyses included testing results across a range of inputs. The model was validated using the published RxPONDER trial data.ResultsIn premenopausal women, the 10-year distant recurrence-free survival rates were 85.3% with chemo-endocrine and 80.1% with endocrine therapy. The estimated life-years and QALYs gained with chemotherapy in premenopausal women were 2.1 and 0.6, respectively. There was no chemotherapy benefit in postmenopausal women. There was no variation in the absolute benefit of chemotherapy across racial or ethnic subgroups. However, there were differences in distant recurrence-free survival rates, life-years, and QALYs across groups. Sensitivity analysis showed similar results. The model closely replicated the RxPONDER trial.ConclusionsModeled population-level outcomes show a small chemotherapy benefit in premenopausal women, but no benefit among postmenopausal women. Simulation modeling provides a useful tool to extend trial data and evaluate population-level outcomes.

Impact of waning immunity against SARS-CoV-2 severity exacerbated by vaccine hesitancy.

The SARS-CoV-2 pandemic has generated a considerable number of infections and associated morbidity and mortality across the world. Recovery from these infections, combined with the onset of large-scale vaccination, have led to rapidly-changing population-level immunological landscapes. In turn, these complexities have highlighted a number of important unknowns related to the breadth and strength of immunity following recovery or vaccination. Using simple mathematical models, we investigate the medium-term impacts of waning immunity against severe disease on immuno-epidemiological dynamics. We find that uncertainties in the duration of severity-blocking immunity (imparted by either infection or vaccination) can lead to a large range of medium-term population-level outcomes (i.e. infection characteristics and immune landscapes). Furthermore, we show that epidemiological dynamics are sensitive to the strength and duration of underlying host immune responses; this implies that determining infection levels from hospitalizations requires accurate estimates of these immune parameters. More durable vaccines both reduce these uncertainties and alleviate the burden of SARS-CoV-2 in pessimistic outcomes. However, heterogeneity in vaccine uptake drastically changes immune landscapes toward larger fractions of individuals with waned severity-blocking immunity. In particular, if hesitancy is substantial, more robust vaccines have almost no effects on population-level immuno-epidemiology, even if vaccination rates are compensatorily high among vaccine-adopters. This pessimistic scenario for vaccination heterogeneity arises because those few individuals that are vaccine-adopters are so readily re-vaccinated that the duration of vaccinal immunity has no appreciable consequences on their immune status. Furthermore, we find that this effect is heightened if vaccine-hesitants have increased transmissibility (e.g. due to riskier behavior). Overall, our results illustrate the necessity to characterize both transmission-blocking and severity-blocking immune time scales. Our findings also underline the importance of developing robust next-generation vaccines with equitable mass vaccine deployment.

Neighborhood-Level Social Determinants of Health and Adolescent Mental Health

ObjectiveMental health diagnoses among adolescents are increasing in prevalence. Existing literature considers associations between individual-level social determinants of health (SDOH) and adolescent mental health. Neighborhood-level SDOH can have a substantial impact on health. This paper examines associations between neighborhood-level SDOH and mental health diagnoses of anxiety, depression, and suicidal ideation among hospitalized adolescents. MethodsWe used 2018 and 2019 Texas Inpatient Discharge Public Use Data Files linked to the zip-code level Child Opportunity Index 2.0, a composite measure of subdomains which characterize neighborhood-level SDOH, to examine rates of mental health diagnoses and associations with patient characteristics across opportunity level quintiles. ResultsThe sample included 50,011 adolescents ages 10–19 admitted to the hospital with the mental health diagnoses anxiety, depression, and/or suicide. Most had a single diagnosis; anxiety (12.9%), depression (37.5%), or suicide (13.0%). Hospitalized adolescents 10–14 years old were a plurality (44.2%) of the sample. Most adolescents were White (64.2%) and non-Hispanic (67.4%) and lived in rural areas (29.6%). Adolescents from racial minority populations and those in rural communities with mental health diagnoses had lower opportunity-levels. Higher opportunity levels were associated with greater odds of having an anxiety or suicide diagnosis while a depression diagnosis was associated with a lower opportunity-level. ConclusionsThere are significant differences in adolescent mental health diagnoses associated with neighborhood opportunity-level. While all adolescents can benefit from mental health education, screening, and early interventions, additional resources tailored to neighborhood-level opportunity may prove a more meaningful way to improve population-level mental health outcomes.

Population health outcomes of blood-based screening for colorectal cancer in comparison to current screening modalities: insights from a discrete-event simulation model incorporating longitudinal adherence

Aim Insufficient adherence to colorectal cancer (CRC) screening impedes individual and population health benefits, with about one-third of individuals non-adherent to available screening options. The impact of poor adherence is inadequately considered in most health economics models, limiting the evaluation of real-world population-level screening outcomes. This study introduces the CAN-SCREEN (Colorectal cANcer SCReening Economics and adherENce) model, utilizing real-world adherence scenarios to assess the effectiveness of a blood-based test (BBT) compared to existing strategies. Materials and methods The CAN-SCREEN model evaluates various CRC screening strategies per 1,000 screened individuals for ages 45–75. Adherence is modeled in two ways: (1) full adherence and (2) longitudinally declining adherence. BBT performance is based on recent pivotal trial data while existing strategies are informed using literature. The full adherence model is calibrated using previously published Cancer Intervention and Surveillance Modeling Network (CISNET) models. Outcomes, including life-years gained (LYG), CRC cases averted, CRC deaths averted, and colonoscopies, are compared to no screening. Results Longitudinal adherence modeling reveals differences in the relative ordering of health outcomes and resource utilization, as measured by the number of colonoscopies performed per 1,000, between screening modalities. BBT outperforms the fecal immunochemical test (FIT) and the multitarget stool DNA (mtsDNA) test with more CRC deaths averted (13) compared to FIT and mtsDNA (7, 11), more CRC cases averted (27 vs. 16, 22) and higher LYG (214 vs. 157, 199). BBT yields fewer CRC deaths averted compared to colonoscopy (13, 15) but requires fewer colonoscopies (1,053 vs. 1,928). Limitations Due to limited data, the CAN-SCREEN model with longitudinal adherence leverages evidence-informed assumptions for the natural history and real-world longitudinal adherence to screening. Conclusions The CAN-SCREEN model demonstrates that amongst non-invasive CRC screening strategies, those with higher adherence yield more favorable health outcomes as measured by CRC deaths averted, CRC cases averted, and LYG.

Pharmacogenetic testing in primary care could bolster depression treatment: A value proposition.

Pharmacogenetic testing could reduce the time to identify a safe and effective medication for depression; however, it is underutilized in practice. Major depression constitutes the most common mental disorder in the US, and while antidepressant therapy can help, the current trial -and error approach can require patients to endure multiple medication trials before finding one that is effective. Tailoring the fit of pharmacogenetic testing with prescribers' needs across a variety of settings could help to establish a generalizable value proposition to improve likelihood of adoption. We conducted a study to explore the value proposition for health systems using pharmacogenetic testing for mental health medications through prescribers' real-world experiences using implementation science concepts and systematic interviews with prescribers and administrators from four health care systems. To identify a value proposition, we organized the themes according to the Triple Aim framework, a leading framework for health care policy which asserts that high-value care should focus on three key metrics: (1) better health care quality and (2) population-level outcomes with (3) reduced per capita costs. Primary care providers whom we interviewed said that they value pharmacogenetic testing because it would provide more information about medications that they can prescribe, expanding their ability to identify medications that best-fit patients and reducing their reliance on referrals to specialists; they said that this capacity would help meet patients' needs for access to mental health care through primary care. At the same time, prescribers expressed differing views about how pharmacogenetic testing can help with quality of care and whether their views about out-of-pocket cost would prevent them from offering it. Thus, implementation should focus on integrating pharmacogenetic testing into primary care and using strategies to support prescribers' interactions with patients.

Pollinator competition and the contingency of nectar depletion during an early spring resource pulse.

Concerns about competition between pollinators are predicated on the assumption of floral resource limitation. Floral resource limitation, however, is a complex phenomenon involving the interplay of resource production by plants, resource demand by pollinators, and exogenous factors-like weather conditions-that constrain both plants and pollinators. In this study, we examined nectar limitation during the mass flowering of rosaceous fruit trees in early spring. Our study was set in the same region as a previous study that found severe nectar limitation in summer grasslands. We used this seasonal contrast to evaluate two alternative hypotheses concerning the seasonal dynamics of floral resource limitation: either (H1) rates of resource production and consumption are matched through seasonal time to maintain a consistent degree of resource limitation, or (H2) a mismatch of high floral resource production and low pollinator activity in early spring creates a period of relaxed resource limitation that intensifies later in the year. We found generally much lower depletion in our spring study compared to the near 100% depletion found in the summer study, but depletion rates varied markedly through diel time and across sampling days, with afternoon depletion rates sometimes exceeding 80%. In some cases, there were also pronounced differences in depletion rates across simultaneously sampled floral species, indicating different degrees of nectar exploitation. These findings generally support the seasonal mismatch hypothesis (H2) but underscore the complex contingency of nectar depletion. The challenge of future work is to discern how the fluctuation of resource limitation across diel, inter-diel, and seasonal time scales translates into population-level outcomes for pollinators.

Observing the Clinical Course of Duchenne Muscular Dystrophy in Medicaid Real-World Healthcare Data.

Duchenne muscular dystrophy (DMD) is a rare, severe progressive neuromuscular disease. Health insurance claims allow characterization of population-level real-world outcomes, based on observed healthcare resource use. An analysis of data specific to those with Medicaid insurance is presently unavailable. The objective was to describe the real-world clinical course of DMD based on claims data from Medicaid-insured individuals in the USA. Individuals with DMD were identified from the MarketScan Multi-State Medicaid datasets (2013-2018). Diagnosis and procedure codes from healthcare claims were used to characterize the occurrence of DMD-relevant clinical observations; categories were scoliosis, cardiovascular-related, respiratory and severe respiratory-related, and neurologic/neuropsychiatric. Age-restricted analyses were conducted to focus on the ages at which DMD-relevant clinical observations were more likely to be captured, and to better understand the impact of both age and follow-up time. Of 2007 patients with DMD identified, median (interquartile range) age at index was 14 (9-20) years, and median follow-up was 3.1 (1.6-4.7) years. Neurologic and neuropsychiatric observations were most frequently identified, among 49.3% of the cohort; followed by cardiovascular (48.5%), respiratory (38.1%), scoliosis (36.3%), and severe respiratory (25.0%). Prevalence estimates for each category were higher when analyzed within age-restricted subgroups; and increased as follow-up time increased. This study is the first to use diagnosis and procedure codes from real-world Medicaid claims to document the clinical course in DMD. Findings were consistent with previously published estimates from commercially insured populations and clinical registries; and contribute to the expanding body of real-world evidence around clinical progression of patients with DMD.

Associating with kin selects for disease resistance and against tolerance.

Behavioural and physiological resistance are key to slowing epidemic spread. We explore the evolutionary and epidemic consequences of their different costs for the evolution of tolerance that trades off with resistance. Behavioural resistance affects social cohesion, with associated group-level costs, while the cost of physiological resistance accrues only to the individual. Further, resistance, and the associated reduction in transmission, benefit susceptible hosts directly, whereas infected hosts only benefit indirectly, by reducing transmission to kin. We therefore model the coevolution of transmission-reducing resistance expressed in susceptible hosts with resistance expressed in infected hosts, as a function of kin association, and analyse the effect on population-level outcomes. Using parameter values for guppies, Poecilia reticulata, and their gyrodactylid parasites, we find that: (1) either susceptible or infected hosts should invest heavily in resistance, but not both; (2) kin association drives investment in physiological resistance more strongly than in behavioural resistance; and (3) even weak levels of kin association can favour altruistic infected hosts that invest heavily in resistance (versus selfish tolerance), eliminating parasites. Overall, our finding that weak kin association affects the coevolution of infected and susceptible investment in both behavioural and physiological resistance suggests that kin selection may affect disease dynamics across systems.

Evaluating population-level outcomes in Chronic Lymphocytic leukemia in the era of novel therapies using the SEER registry

In the last decade, novel agents such as BTK and BCL-2 inhibitors have revolutionized treatment of CLL/SLL, with clinical trials showing improved overall survival compared to chemotherapeutic agents. However, studies examining whether they have improved overall survival at the population level are lacking. We evaluated this by conducting a retrospective analysis of CLL/SLL patients registered in the National Cancer Institute’s surveillance epidemiology and end results (SEER) database, analyzing overall survival (OS) in periods pre- and post-availability of novel agents, along with demographic information. Our results showed that median OS significantly improved over time [7.8 years (2000–2005), 9.1 years (2006–2013), and not reached (2014–2018) (p < 0.001)]. Compared to diagnosis in 2014–2018, diagnosis in earlier periods was associated with higher mortality risk (2000–2005-HR 1.32, 95 % CI 1.28–1.37, p < 0.001: 2006–2013-HR 1.09, 95 % CI 1.06–1.13, p < 0.001). Lower mortality risk was seen in patients age < 85 years whereas median household income of <$75000 was associated with higher mortality. Our study provides real-world data suggesting a possible multifactorial contribution to improvement in survival, including availability of novel agents, better monitoring, and supportive care. They also show discrepancies in overall survival for CLL/SLL patients due to socioeconomic status and demographic factors.

Diagnosis Shift in Site of Origin of Tubo-Ovarian Carcinoma.

To assess population-level trends, characteristics, and outcomes of high-grade serous tubo-ovarian carcinoma in the United States. This retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 27,811 patients diagnosed with high-grade serous tubo-ovarian carcinoma from 2004 to 2020. The exposure was the primary cancer site (ovary or fallopian tube). Main outcome measures were temporal trends, clinical characteristics, and overall survival associated with primary cancer site assessed in multivariable analysis. The study population comprised 23,967 diagnoses of high-grade serous ovarian carcinoma and 3,844 diagnoses of high-grade serous fallopian tubal carcinoma. The proportion of diagnoses of high-grade serous fallopian tubal carcinoma increased from 365 of 7,305 (5.0%) in 2004-2008 to 1,742 of 6,663 (26.1%) in 2017-2020. This increase was independent in a multivariable analysis (adjusted odds ratio [aOR] vs 2004-2008, 2.28 [95% CI, 1.98-2.62], 3.27 [95% CI, 2.86-3.74], and 6.65 [95% CI, 5.84-7.57] for 2009-2012, 2013-2016, and 2017-2020, respectively). This increase in high-grade serous fallopian tubal carcinoma was seen across age groups (4.3-5.8% to 22.7-28.3%) and across racial and ethnic groups (4.1-6.0% to 21.9-27.5%) (all P for trend <.001). Among the cases of tumors smaller than 1.5 cm, the increase was particularly high (16.9-67.6%, P for trend <.001). Primary-site tumors in the high-grade serous fallopian tubal carcinoma group were more likely to be smaller than 1.5 cm (aOR 8.26, 95% CI, 7.35-9.28) and unilateral (aOR 7.22, 95% CI, 6.54-7.96) compared with those in high-grade serous ovarian carcinoma. At the cohort level, the diagnosis shift to high-grade serous fallopian tubal carcinoma was associated with narrowing differences in survival over time between the two malignancy groups: adjusted hazard ratio 0.84 (95% CI, 0.74-0.96), 0.91 (95% CI, 0.82-1.01), 1.01 (95% CI, 0.92-1.12), and 1.12 (95% CI, 0.98-1.29) for 2004-2008, 2009-2012, 2013-2016, and 2017-2020, respectively. This population-based assessment suggests that diagnoses of high-grade serous tubo-ovarian carcinoma in the United States have been rapidly shifting from high-grade serous ovarian to fallopian tubal carcinoma in recent years, particularly in cases of smaller, unilateral tumors.

Improving patient outcomes while reducing readmissions with data analytics

As post-acute care spend continues to rise and the Centers for Medicare and Medicaid Services (CMS) moves forward with promoting both value-based and risk-bearing models of care, it is essential for accountable care organisations (ACOs), payers and hospital providers to take proactive measures to find innovative and data-driven strategies to meet the future demands of healthcare. Yet disparate electronic health record (EHR) systems between acute and post-acute providers continue to pose challenges in the ability to access live patient data across care settings, which enables clinical line of sight to manage both patient and population-level quality outcomes. Utilisation of an EHR-agnostic platform, which mitigates interoperability issues, can improve care transitions, provide data analytics to manage the patient care journey, foster seamless implementation of standardised care pathways and ultimately reduce total costs within post-acute networks by decreasing readmissions and length of stay. St. Joseph’s Health implemented such a data analytics platform and instituted a post-acute nurse navigator, social worker and care manager roles to manage their value-based patients in the postacute setting. As a result, their Medicare Shared Savings Plan ACO, Mission Health Coordinated Care, achieved a significant reduction in readmissions from 24 per cent to 17.8 per cent, as well as a total cost of care savings of US$1.6m in its first year. Currently, the readmission rate is down to 13.6 per cent, and there has also been a 3.2-day reduction in average length of stay. Owing to their successful post-acute strategy and programming, the project was scaled to include all patients in value-based contracts.