Burden Metrics Research Articles

Coronary Plaque Radiomic Phenotypes Predict Fatal or Nonfatal Myocardial Infarction: Analysis of the SCOT-HEART Trial

BackgroundCoronary computed tomography (CT) angiography–derived attenuation-based plaque burden assessments can identify patients at risk of myocardial infarction. ObjectivesThis study sought to assess whether more detailed plaque morphology assessment using patient-based radiomic characterization could further enhance the identification of patients at risk of myocardial infarction during long-term follow-up. MethodsPost hoc analysis of coronary CT angiography was performed within the SCOT-HEART (Scottish Computed Tomography of the HEART) clinical trial. Coronary plaque segmentations were used to calculate plaque burdens and eigen radiomic features that described plaque morphology. Univariable and multivariable Cox proportional hazard models were used to evaluate the association between clinical and image-based features and fatal or nonfatal myocardial infarction, whereas Harrell’s C-statistic and cumulative/dynamic area under the curve (AUC) values with cross-validation were used to evaluate prognostic performance. ResultsScans from 1,750 patients (aged 58 ± 9 years; 56% male) were analyzed. Over a median of 8.6 years of follow-up, 82 patients had a fatal or nonfatal myocardial infarction. Among the eigen radiomic features, 15 were associated with myocardial infarction in univariable analysis, and 8 features retained their association following adjustment for cardiovascular risk score and plaque burden metrics. Adding plaque burden metrics to a clinical model incorporating cardiovascular risk score, Agatston score and presence of obstructive coronary artery disease had similar prediction performance (C-statistic 0.70 vs 0.70), whereas further addition of eigen radiomic features improved model performance (C-statistic 0.74). In temporal analysis, the model including eigen radiomic features had higher cumulative/dynamic AUC values following the fifth year of follow-up. ConclusionsRadiomics-based precision phenotyping of coronary plaque morphology provided improvements to long-term prediction of myocardial infarction by CT angiography over and above clinical factors and plaque burden. (Scottish Computed Tomography of the HEART [SCOT-HEART]; NCT01149590)

Urgent palliative care: An effective intervention to improve end-of-life experience and outcomes for patients with advanced cancer.

203 Background: Early integration of palliative care services for advanced oncology patients has a well-documented benefit on quality-of-life measures including symptom management, quality-of-death measures, cost-effectiveness, care-giver burden, and patient satisfaction metrics. However many barriers exist, including delayed referrals and negative perceptions of hospice/palliative care by patients and families. Furthermore, wait times from referral to visit can vary from weeks to months. For patients with late-stage disease, rapidly advancing disease or symptoms, this delay can lead to unnecessary acute care utilization, impoverished quality-of-life, and discordant end-of-life care. Methods: The CU Cancer Center CARE clinic provides advanced symptom management and urgent care services to oncology patients, often seeing patients with high symptom burden and advanced disease. A recent unpublished case-based analysis demonstrated that patients seen in CARE clinic 4 times or more in a month have a high risk of inpatient mortality within 3 months. In response, the CARE clinic created an urgent palliative care program wherein patients have the ability to see a palliative care provider within 1 week of referral who could provide ongoing advanced symptom management/medication titration and facilitate conversations around goal-concordant care in late-stage illness. A 1-year feasibility pilot took place from 2022-2023. Referrals required patients to meet the following criteria: 1) Not already being seen by an ambulatory palliative care professional; and 2) any of the following: prognosis of weeks without an end-of-life care plan; symptoms likely to require hospitalization if not addressed within a week; or seen in CARE clinic 4 or more times in the last month From 09/2022-08/2023, 55 patients were seen. Outcomes were followed for 3 months following final CARE clinic visit and were compared to patients who had received palliative care referrals from the CARE clinic in the preceding year (9/2021-9/2022). Results: In-hospital deaths, hospital days in the last 30 days of life, and palliative care/hospice involvement were all positively affected in our initial pilot. Notably, in-hospital deaths were reduced by 50%. There was also a 14% increase in deaths with hospice care in the pilot group compared to the control group. Conclusions: Data from this feasibility pilot suggest that urgent palliative care can improve key metrics in oncology quality-of-care, and improve cost effectiveness. Further delineation of the outcomes compared in a rigorously controlled population will further define the relative clinical benefit and fiscal implications of such interventions. Urgent palliative care outcomes. Historical Control (2021-2022) Pilot (2022-2023) N 44 55 Hospitalizations 101 52 Deaths 30 (68%) 40 (72%) Deaths in the Hospital 8 (18%) 5 (9%) Deaths With Hospice Care 21 (47%) 34 (61%)

Global Burden Disease Estimates for Major Depressive Disorders (MDD): Areview of diagnosticinstruments used in studies ofprevalence.

Global Burden of Disease (GBD) estimates have significant policy implications nationally and internationally. Disease burden metrics, particularly for depression, have played a critical role in raising governmental awareness of mental health and in calculating the economic cost of depression. Recently, the World Health Organization ranked depression as the single largest contributor to global disability. The main aim of this paper was to assess the basis upon which GBD prevalence estimates for major depressive disorder (MDD) were made. We identify the instruments used in the 2019 GBD estimates and provide a descriptive assessment of the five most frequently used instruments. The majority of country studies, 356/566 (62.9%), used general mental health screeners or structured/semi-structured interview guides, 98/566 (17.3%) of the studies used dedicated depression screeners, and 112 (19.8%) used other tools for assessing depression. Thus, most of the studies used instruments that were not designed to make a diagnosis of depression or assess depression severity. Our results are congruent with and extend previous research that has identified critical flaws in the data underpinning the GBD estimates for MDD. Despite the widespread promotion of these prevalence estimates, caution is needed before using them to inform public policy and mental health interventions. This is particularly important in lower-income countries where resources are scarce.

Sport-related concussions in baseball and softball: do mechanisms of injury affect recovery?

Baseball and softball pose unique risks for sport-related concussion (SRC). Although these are not collision sports, concussions in baseball and softball can nonetheless involve high-speed impacts. In a regional, single-institution cohort of baseball and softball athletes who sustained an SRC, the current study sought to 1) describe the mechanisms of injury that led to SRC, and 2) compare initial symptom burden and recovery metrics across mechanisms, including time to return to learn (RTL), time to symptom resolution, and time to return to play (RTP) by mechanism of injury. A retrospective cohort study was performed of baseball and softball athletes 12 to 23 years old who sustained an SRC between November 2017 and April 2022. Mechanisms of injury were divided into two categories: 1) contact mechanism (i.e., what initiated contact with the injured player, such as head-to-ball), and 2) player mechanism (i.e., the action the injured player was performing at the time of injury, such as fielding). The recovery outcomes of time to RTL, symptom resolution, and RTP were compared between mechanisms using bivariate analysis and multivariable regression analysis, controlling for sex, age, time to present to concussion clinic, and initial total symptom score. The sample included 58 baseball and softball players (60.3% female, mean age 16.0 ± 1.9 years). Most SRCs (62.1%) occurred during competition. Head-to-ball (50.0%) was the most common contact mechanism, followed by head-to-head/body (31.0%) and head-to-wall/ground/equipment (17.2%). Fielding (63.8%) was the most common player mechanism, followed by drills (20.7%) and running (13.8%). SRCs sustained in practice had significantly longer RTL (median 10.0 [interquartile range (IQR) 3.3-16.3] vs 4.0 [IQR 2.0-8.0] days; U = 421.5, p = 0.031) and symptom resolution (37.0 [IQR 18.0-90.0] vs 14.0 [IQR 7.0-41.0] days; U = 406.5, p = 0.025) compared with SRCs sustained in competition. Multivariable regression analysis revealed that head-to-wall/ground/equipment contact mechanism was associated with longer RTL (β = 0.30, 95% CI 0.07-0.54, p = 0.013). The current study found that SRCs in baseball and softball occurred more often in competition than in practice. Head-to-ball and fielding were the most common contact and player mechanisms, respectively. SRCs sustained in practice were associated with longer time to RTL and symptom resolution, and head-to-wall/ground/equipment was associated with longer RTL in multivariable regression analysis. These results provide empirical data to improve concussion safety in baseball/softball.

A Metric of Societal Burden Based on Virus Succession to Determine Economic Losses and Health Benefits of China's Lockdown Policies: Model Development and Validation.

The COVID-19 pandemic had a profound impact on the global health system and economic structure. Although the implementation of lockdown measures achieved notable success in curbing the spread of the pandemic, it concurrently incurred substantial socioeconomic costs. The objective of this study was to delineate an equilibrium between the economic losses and health benefits of lockdown measures, with the aim of identifying the optimal boundary conditions for implementing these measures at various pandemic phases. This study used a model to estimate the half-lives of the observed case fatality rates of different strains. It was based on global infection and death data collected by the World Health Organization and strain sequence time series data provided by Nextstrain. The connection between the health benefits and economic losses brought by lockdown measures was established through the calculation of disability-adjusted life years. Taking China's city lockdowns as an example, this study determined the cost-benefit boundary of various lockdown measures during the evolution of COVID-19. The study reveals a direct proportionality between economic losses due to lockdowns and the observed case fatality rates of virus strains, a relationship that holds true irrespective of population size or per capita economic output. As SARS-CoV-2 strains evolve and population immunity shifts, there has been a notable decrease in the observed case fatality rate over time, exhibiting a half-life of roughly 8 months. This decline in fatality rates may offset the health benefits of maintaining unchanged lockdown measures, given that the resultant economic losses might exceed the health benefits. The initial enforcement of lockdown in Wuhan led to significant health benefits. However, with the decline in the observed case fatality rate of the virus strains, the economic losses increasingly outweighed the health benefits. Consequently, it is essential to consistently refine and enhance lockdown strategies in accordance with the evolving fatality and infection rates of different virus strains, thereby optimizing outcomes in anticipation of future pandemics.

Neuropsychological Test Performance Differentiates Subgroups of Individuals With Adult Moyamoya Disease: A Cross-Sectional Clinical Study.

Moyamoya disease (MMD) is a rare noninflammatory disorder involving progressive intracranial vasculopathy and impaired cerebral blood flow in the anterior circulation, resulting in stroke and cognitive impairment. We aimed to characterize cognitive impairment and the possible predictive value of sociodemographic and clinical characteristics of adults with MMD. This cross-sectional study examined neurocognitive performance in a group of 42 consecutive adult patients (mean age = 40.52 years; 69% female) referred for a presurgical neuropsychological evaluation. Neuropsychological functioning was assessed with a comprehensive battery, and cognitive dysfunction was defined as 1.5 SDs below the mean. Neurocognitive performance correlated with clinical/demographic characteristics and disease markers. Most patients (91%) had a history of stroke, and 45% had cognitive deficits, most notably on measures of attention/speed (48%), executive functioning (47%), visuoconstruction (41%), and memory (31%-54%). Only higher educational attainment and poor collateral blood flow in the right hemisphere differentiated cognitively impaired (n = 19) and intact groups (n = 23), and MMD-related characteristics (eg, disease duration, stroke history) did not differentiate the 2 groups. Consistent with previous work, frontal-subcortical cognitive deficits (eg, deficits in mental speed, attention, executive functioning) were found in nearly half of patients with MMD and better cognitive performance was associated with factors related to cognitive reserve. Angiographic metrics of disease burden (eg, Suzuki rating, collateral flow) and hemodynamic reserve were not consistently associated with poorer cognitive outcomes, suggesting that cognition is a crucial independent factor to assess in MMD and has relevance for treatment planning and functional status.

Global, regional, and national cancer burdens of respiratory and digestive tracts in 1990–2044: A cross-sectional and age-period-cohort forecast study

BackgroundUnderstanding the current status and future trends of cancer burdens by systems provides important information for specialists, policymakers, and specific risk populations. MethodsThe aim of this study was to compare the current and future cancer burdens of the gastrointestinal (GI) and respiratory tracts in terms of their magnitude and distribution. Data from a total of eight cancers of the digestive and respiratory tracts in the Global Burden of Disease (GBD) database were collected. The age-standardized incidence/death rates (ASIR/ASDRs), disability-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs) were analyzed. Future trends were predicted with Bayesian age-period-cohort (BAPC) and NORDPRED models. ResultsIn 2019, there was a significant increase in DALY for both digestive and respiratory tract cancers compared to 1990. Meanwhile, ASIR increased slightly and ASDR decreased notably. In 2019, the global cancer burdens of respiratory and digestive tracts were 38568363.53 and 66912328.72 in DALY, 34.28 and 55.32 in ASIR, and 656.82 and 808.22 in ASDR per 100,000 population with changes of +54.63% and +43.93%, +2.92% and +5.65%, and −17.39% and −26.83% compared to those in 1990, respectively. Significant cross-regional differences in the cancer burdens were observed among the regions. Compared to four representative chronic diseases, the burden of cancers showed less remission and greater global inequalities. The burdens of both digestive and respiratory tract cancers were higher in males than in females in terms of the ASIR, ASDR, and DALY. The incidence and mortality rates of respiratory tract cancers were up to 3–4 times higher in males than in females, whereas the difference between male and female rates of digestive tract cancers was relatively smaller. The main risk factor associated with all kinds of digestive and respiratory tract cancers is tobacco, leading to 18.5 in ASDR and 3.38×107 in DALY for respiratory tract cancers; 8.29 in ASDR and 1.60×107 in DALY for digestive tract cancers, in 2019. Additionally, alcohol use contributes to most digestive and respiratory tract cancers (1.23/1.03 in ASDR and 1.60×106/2.57×106 in DALY for respiratory tract cancers; 4.19/3.82 in ASDR and 4.49×106/8.06×106 in DALY for digestive tract cancers), except for stomach cancer and tracheal, bronchus, and lung cancer. The cancer burdens of respiratory and digestive tracts are likely to decrease substantially between 2020 and 2044. For most metrics, except for the ASIR and male-to-female ratios of ASDR and ASDALY in digestive tract cancers, the worldwide variances of burden metrics have been decreasing in the past decades and will possibly maintain stable trends in the future. ConclusionsThe epidemiology of respiratory and GI tract cancers has common features and individual characteristics that are reflected in geography, age characteristics, and risk factors. Current epidemiological status, future trends, and the globalization of these disease burdens are important factors for making scientific planning of resources to minimize the cancer burden metrics and their cross-regional inequalities.

Potential determinants of nocturnal hypoxemic burden and its association with atrial fibrillation recurrence after catheter ablation

Abstract Background Sleep-disordered breathing (SDB) is present in approximately half of patients with atrial fibrillation (AF) scheduled for catheter ablation (CA) and coincides with an elevated nocturnal hypoxemia. Purpose To evaluate determinants of nocturnal hypoxemic burden metrics and its association with AF recurrence after CA in patients undergoing a systematic SDB management and treatment pathway. Methods Consecutive AF patients scheduled for CA without history of SDB and/or SDB screening were included. Patients were referred to a virtual SDB management pathway including mobile health supported overnight home sleep test. An apnoea-hypopnoea index (AHI) of 5 to <15 and ≥ 15 were interpreted as mild and moderate-to-severe SDB, respectively. Oximetry data from home sleep tests were analyzed by a computer algorithm to evaluate metrics of nocturnal hypoxemic burden: time spent below 90% oxygen desaturation (T90) based on acute desaturations (T90 desat) or non-specific drifts in oxygen desaturation (T90 non-spec). Patients were monitored for AF recurrences through standard 12-lead ECG or Holter ECG and/or smartphone-based photophletysmography (PPG) performed at 3- and 12-month follow up. Multiple regression analysis was employed to (1) evaluate determinants of nocturnal hypoxemic burden metrics and (2) identify predictors of AF recurrence during 12 months after CA (excluding 3 months blanking period). Results The analysis included 210 patients (42% female, mean age 64± 9 years). Median AHI was 14.7 [6.7-24.7], median T90desat was 0.25 [0.03-1.42] minutes, T90non-spec 0.26 [0.08-0.78] minutes. Overall, 101 (48%) patients were diagnosed with moderate-to-severe SDB and 68 (32%) had mild SDB. Of patients with moderate-to- severe SDB and mild SDB, 87% and 46%, respectively, received a SDB therapy recommendation. Multiple linear regression analysis identified diabetes mellitus (B 8.611 95%CI 1.350-15.871, p=0.020) and AHI ≥ 15 (B 5.886, 95%CI 1.793-9.979, p= 0.005) as predictors of T90non-spec. Thyroid dysfunction (B 1.849, 95%CI 0.623-3.075, p=0.003) and AHI ≥ 15 (B 2.161, 95%CI 1.320-3.001, p<0.001) were significant predictors of T90desat. During 12 months after CA, 65 (31%) patients had experienced at least one AF recurrence after the blanking period. After multiple Cox-regression, age (HR 1.032, 95%CI 1.002-1.063, p= 0.035) and BMI ≥ 25 (HR 2.029, 95%CI 1.032-3.989, p=0.040) remained predictors for AF recurrences. Conclusions In AF patients scheduled for CA, SDB (AHI ≥ 15) and thyroid dysfunction were predictors for nocturnal hypoxemic burden with repetitive desaturations (T90desat). SDB and diabetes mellitus were predictors for nocturnal hypoxemic burden without repetitive desaturations (T90non-spec). In patients with AF who followed a virtual SDB management and treatment pathway, SDB presence and nocturnal hypoxemic burden metrics did not emerge as predictors, whereas age and BMI (≥25) remained significant predictors for AF recurrence.

Does socioeconomic and environmental burden affect vulnerability to extreme air pollution and heat? A case-crossover study of mortality in California.

Extreme heat and air pollution is associated with increased mortality. Recent evidence suggests the combined effects of both is greater than the effects of each individual exposure. Low neighborhood socioeconomic status ("socioeconomic burden") has also been associated with increased exposure and vulnerability to both heat and air pollution. We investigated if neighborhood socioeconomic burden or the combination of socioeconomic and environmental exposures ("socioenvironmental burden") modified the effect of combined exposure to extreme heat and particulate air pollution on mortality in California. We used a time-stratified case-crossover design to assess the impact of daily exposure to extreme particulate matter <2.5 μm (PM2.5) and heat on cardiovascular, respiratory, and all-cause mortality in California 2014-2019. Daily average PM2.5 and maximum temperatures based on decedent's residential census tract were dichotomized as extreme or not. Census tract-level socioenvironmental and socioeconomic burden was assessed with the CalEnviroScreen (CES) score and a social deprivation index (SDI), and individual educational attainment was derived from death certificates. Conditional logistic regression was used to estimate associations of heat and PM2.5 with mortality with a product term used to evaluate effect measure modification. During the study period 1,514,292 all-cause deaths could be assigned residential exposures. Extreme heat and air pollution alone and combined were associated with increased mortality, matching prior reports. Decedents in census tracts with higher socioenvironmental and socioeconomic burden experienced more days with extreme PM2.5 exposure. However, we found no consistent effect measure modification by CES or SDI on combined or separate extreme heat and PM2.5 exposure on odds of total, cardiovascular or respiratory mortality. No effect measure modification was observed for individual education attainment. We did not find evidence that neighborhood socioenvironmental- or socioeconomic burden significantly influenced the individual or combined impact of extreme exposures to heat and PM2.5 on mortality in California. We investigated the effect measure modification by socioeconomic and socioenvironmental of the co-occurrence of heat and PM2.5, which adds support to the limited previous literature on effect measure modification by socioeconomic and socioenvironmental burden of heat alone and PM2.5 alone. We found no consistent effect measure modification by neighborhood socioenvironmental and socioeconomic burden or individual level SES of the mortality association with extreme heat and PM2.5 co-exposure. However, we did find increased number of days with extreme PM2.5 exposure in neighborhoods with high socioenvironmental and socioeconomic burden. We evaluated multiple area-level and an individual-level SES and socioenvironmental burden metrics, each estimating socioenvironmental factors differently, making our conclusion more robust.

Empowerment-Led Guided Self-Help Intervention for Symptom Burden in Breast Cancer Women Treated With Ovarian Function Suppression: A Randomized Trial Protocol.

Ovarian function suppression (OFS) treatment causes breast cancer patients' estrogens to fall rapidly to postmenopausal levels, and the 5-year treatment duration and 28-day treatment cycles place a heavy physical and psychological symptom burden on them, which in turn directly or indirectly affects the survival benefit. Managing symptom burden early in treatment is critical, but OFS-related studies have yet to be seen. Self-management is essential for patients' symptom burden. However, self-help management is hampered by patients' lack of knowledge, skills, motivation, etc. Guided self-help intervention (GSH) provides a feasible approach. Empowerment theory is a promising theoretical framework to guide self-management. A prospective two-arm parallel randomized controlled single-blind clinical trial will be conducted to investigate the effect of symptom burden GSH based on empowerment theory in breast cancer patients in the early stages of OFS treatment. A block randomization method is used to allocate 144 patients to either the control or intervention group. The program is conducted according to the OFS return-to-hospital treatment cycle. The intervention group will receive a total of two rounds and five sessions of empowering GSH, lasting at least 15 weeks in total; the control group will receive only usual nursing care. Symptom burden and related metrics will be assessed at baseline and 1, 3, and 6 months after OFS treatment, and changes between and within groups will be explored. This paper adhered to the SPIRIT and CONSORT guidelines. These results will help to validate the GSH in symptom burden management for breast cancer patients in OFS treatment early stages. It enriches its symptom burden management research and may provide implications for the whole cycle of OFS treatment patients.

Burden of female breast cancer in India: estimates of YLDs, YLLs, and DALYs at national and subnational levels based on the national cancer registry programme.

Female breast cancer (BC) is the leading cause of cancer incidence and mortality in India, andaccounted for 13.5% of new cancer cases and 10% of cancer-related deaths in 2020. This study aims to estimate and report the female BC burden in India at state level from 2012 to 2016 in terms of years of life lost, years lived with disability, and disability-adjusted life years (DALYs), and to project the burden for the year 2025. The cancer incidence and mortality data from 28 population-based cancer registrieswere analysed. The mean mortality to incidence ratio was estimated, and mortality figures were adjusted for underreporting. The burden of female BC was estimated at national and subnational levels using Census data, World Health Organisation's lifetables, disability weights, and the DisMod-II tool. A negative binomial regression is employed to project burden for 2025. The burden of BC among Indian women in 2016 was estimated to be 515.4 DALYs per 100,000 women after age standardization. The burden metrics at state level exhibited substantial heterogeneity. Notably, Tamil Nadu, Telangana, Karnataka, and Delhi had a higher burden of BC than states in the eastern and north-eastern regions. The projection for 2025 indicates to a substantial increase, reaching 5.6 million DALYs. The female BC burden in India was significantly high in 2016 and is expected to substantially increase. Undertaking a multidisciplinary, context-specific approach for its prevention and controlcan address this rising burden.

Histologic tau lesions and magnetic resonance imaging biomarkers differ across two progressive supranuclear palsy variants.

Progressive supranuclear palsy is a neurodegenerative disease characterized by the deposition of four-repeat tau in neuronal and glial lesions in the brainstem, cerebellar, subcortical and cortical brain regions. There are varying clinical presentations of progressive supranuclear palsy with different neuroimaging signatures, presumed to be due to different topographical distributions and burden of tau. The classic Richardson syndrome presentation is considered a subcortical variant, whilst progressive supranuclear palsy with predominant speech and language impairment is considered a cortical variant, although the pathological underpinnings of these variants are unclear. In this case-control study, we aimed to determine whether patterns of regional tau pathology differed between these variants and whether tau burden correlated with neuroimaging. Thirty-three neuropathologically confirmed progressive supranuclear palsy patients with either the Richardson syndrome (n = 17) or speech/language (n = 16) variant and ante-mortem magnetic resonance imaging were included. Tau lesion burden was semi-quantitatively graded in cerebellar, brainstem, subcortical and cortical regions and combined to form neuronal and glial tau scores. Regional magnetic resonance imaging volumes were converted to Z-scores using 33 age- and sex-matched controls. Diffusion tensor imaging metrics, including fractional anisotropy and mean diffusivity, were calculated. Tau burden and neuroimaging metrics were compared between groups and correlated using linear regression models. Neuronal and glial tau burden were higher in motor and superior frontal cortices in the speech/language variant. In the subcortical and brainstem regions, only the glial tau burden differed, with a higher burden in globus pallidus, subthalamic nucleus, substantia nigra and red nucleus in Richardson's syndrome. No differences were observed in the cerebellar dentate and striatum. Greater volume loss was observed in the motor cortex in the speech/language variant and in the subthalamic nucleus, red nucleus and midbrain in Richardson's syndrome. Fractional anisotropy was lower in the midbrain and superior cerebellar peduncle in Richardson's syndrome. Mean diffusivity was greater in the superior frontal cortex in the speech/language variant and midbrain in Richardson's syndrome. Neuronal tau burden showed associations with volume loss, lower fractional anisotropy and higher mean diffusivity in the superior frontal cortex, although these findings did not survive correction for multiple comparisons. Results suggest that a shift in the distribution of tau, particularly neuronal tau, within the progressive supranuclear palsy network of regions is driving different clinical presentations in progressive supranuclear palsy. The possibility of different disease epicentres in these clinical variants has potential implications for the use of imaging biomarkers in progressive supranuclear palsy.

Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

NGS-determined molecular markers and disease burden metrics from ctDNA correlate with PFS in previously untreated DLBCL

Personalized risk stratification and treatment may help improve outcomes among patients with diffuse large B-cell lymphoma (DLBCL). We developed a next-generation sequencing (NGS)-based method to assess a range of potential prognostic indicators, and evaluated it using pretreatment plasma samples from 310 patients with previously untreated DLBCL from the GOYA trial (NCT01287741). Variant calls and DLBCL subtyping with the plasma-based method were concordant with corresponding tissue-based methods. Patients with a tumor burden greater than the median (p = .003) and non-germinal center B-cell-like (non-GCB) DLBCL (p = .049) had worse progression-free survival than patients with a tumor burden less than the median or GCB DLBCL. Multi-factor assessment combining orthogonal features from a single pretreatment plasma sample has promise as a prognostic indicator in this setting (p = .085). This minimally invasive plasma-based NGS assay could enable comprehensive prognostic assessment of patients in a clinical setting, with greater accessibility than current methods.

Sleep and Caregiver Burden Among Caregivers of Persons Living With Dementia: A Scoping Review.

Caregivers of persons with dementia report worse sleep when compared to the general population. The objective of this review was to synthesize evidence regarding the link between caregiver burden and dementia caregivers' sleep. We conducted a scoping review using a systematic search for pertinent literature in PubMed, CINAHL, and Web of Science through March 2022. Keywords included content areas of dementia, caregiver burden, and sleep. Inclusion criteria were informal caregivers of persons living with dementia, a measured relationship between informal dementia caregiver sleep and subjective caregiver burden variables, and original research. Non-English studies were excluded. Extracted data were organized in tables, compared, and synthesized. The search yielded 540 nonduplicate articles screened by title and abstract; 118 full-text articles were reviewed; 24 were included. Most studies were cross-sectional, with variable sample sizes. Dementia caregivers had significantly poorer overall perceived sleep than noncaregivers across 4 studies that examined self-reported sleep measures. Eighteen studies investigated the association between caregiver burden and self-reported sleep quality, with 14 reporting a significant positive association between caregiver burden and self-reported sleep quality, and 4 finding null results. Only 2 of the 4 studies reporting the association between caregiver burden and objective sleep parameters (ie, actigraphy and polysomnography) reported a significant positive association for at least one sleep subdomain. Although subjective sleep quality is commonly affected by dementia caregiving burden, there is a lack of corresponding evidence on the relationship between burden and objective sleep metrics. Healthcare providers should consider the dementia caregiver burden's impact on sleep and regularly assess caregivers' sleep difficulties. Future studies should focus on consistently measuring caregiver burden and sleep to promote dementia caregiver health and well-being.

Inhaled medications for chronic obstructive pulmonary disease predict surgical complications and survival in stage I non-small cell lung cancer.

Lung function is routinely assessed prior to surgical resection for non-small cell lung cancer (NSCLC). Further assessment of chronic obstructive pulmonary disease (COPD) using inhaled COPD medications to determine disease severity, a readily available metric of disease burden, may predict postoperative outcomes and overall survival (OS) in lung cancer patients undergoing surgery. We retrospectively evaluated clinical stage I NSCLC patients receiving surgical treatment within the Veterans Health Administration from 2006-2016 to determine the relationship between number and type of inhaled COPD medications (short- and long-acting beta2-agonists, muscarinic antagonists, or corticosteroids prescribed within 1 year before surgery) and postoperative outcomes including OS using multivariable models. We also assessed the relationship between inhaled COPD medications, disease severity [measured by forced expiratory volume in 1 second (FEV1)], and diagnosis of COPD. Among 9,741 veterans undergoing surgery for clinical stage I NSCLC, patients with COPD were more likely to be prescribed inhaled medications than those without COPD [odds ratio (OR) =5.367, 95% confidence interval (CI): 4.886-5.896]. Increased severity of COPD was associated with increased number of prescribed inhaled COPD medications (P<0.0001). The number of inhaled COPD medications was associated with prolonged hospital stay [adjusted OR (aOR) =1.119, 95% CI: 1.076-1.165), more major complications (aOR =1.117, 95% CI: 1.074-1.163), increased 90-day mortality (aOR =1.088, 95% CI: 1.013-1.170), and decreased OS [adjusted hazard ratio (aHR) =1.061, 95% CI: 1.042-1.080]. In patients with FEV1 ≥80% predicted, greater number of prescribed inhaled COPD medications was associated with increased 30-day mortality (aOR =1.265, 95% CI: 1.062-1.505), prolonged hospital stay (aOR =1.130, 95% CI: 1.051-1.216), more major complications (aOR =1.147, 95% CI: 1.064-1.235), and decreased OS (aHR =1.058, 95% CI: 1.022-1.095). When adjusting for other drug classes and covariables, short-acting beta2-agonists were associated with increased 90-day mortality (aOR =1.527, 95% CI: 1.120-2.083) and decreased OS (aHR =1.087, 95% CI: 1.005-1.177). In patients with early-stage NSCLC, inhaled COPD medications prescribed prior to surgery were associated with both short- and long-term outcomes, including in patients with FEV1 ≥80% predicted. Routine assessment of COPD medications may be a simple method to quantify operative risk in early-stage NSCLC patients.

Comparison of new computational methods for spatial modelling of malaria

BackgroundGeostatistical analysis of health data is increasingly used to model spatial variation in malaria prevalence, burden, and other metrics. Traditional inference methods for geostatistical modelling are notoriously computationally intensive, motivating the development of newer, approximate methods for geostatistical analysis or, more broadly, computational modelling of spatial processes. The appeal of faster methods is particularly great as the size of the region and number of spatial locations being modelled increases.MethodsThis work presents an applied comparison of four proposed ‘fast’ computational methods for spatial modelling and the software provided to implement them—Integrated Nested Laplace Approximation (INLA), tree boosting with Gaussian processes and mixed effect models (GPBoost), Fixed Rank Kriging (FRK) and Spatial Random Forests (SpRF). The four methods are illustrated by estimating malaria prevalence on two different spatial scales—country and continent. The performance of the four methods is compared on these data in terms of accuracy, computation time, and ease of implementation.ResultsTwo of these methods—SpRF and GPBoost—do not scale well as the data size increases, and so are likely to be infeasible for larger-scale analysis problems. The two remaining methods—INLA and FRK—do scale well computationally, however the resulting model fits are very sensitive to the user’s modelling assumptions and parameter choices. The binomial observation distribution commonly used for disease prevalence mapping with INLA fails to account for small-scale overdispersion present in the malaria prevalence data, which can lead to poor predictions. Selection of an appropriate alternative such as the Beta-binomial distribution is required to produce a reliable model fit. The small-scale random effect term in FRK overcomes this pitfall, but FRK model estimates are very reliant on providing a sufficient number and appropriate configuration of basis functions. Unfortunately the computation time for FRK increases rapidly with increasing basis resolution.ConclusionsINLA and FRK both enable scalable geostatistical modelling of malaria prevalence data. However care must be taken when using both methods to assess the fit of the model to data and plausibility of predictions, in order to select appropriate model assumptions and parameters.

Analytics of long-term premature ventricular complexes using an insertable cardiac monitor

Abstract Background Premature ventricular complexes (PVC) are associated with the development of cardiomyopathy, heart failure and pro-arrhythmia. PVC detection using insertable cardiac monitor (ICM) signal processing has recently been introduced. An ICM device capable of monitoring PVC burden over a longer period can be a useful tool for evaluating long-term PVC burden trends. Purpose This study evaluated the various long-term PVC burden trends from patients with implanted ICM capable of continuous PVC burden monitoring. Methods The ICM implemented PVC detection algorithm uses various combinations of long-short-long RR interval sequence and similarity and differences in R-wave morphology for three consecutive beats to detect single PVC events. For this study, long-term daily PVC burden trends from real-world patients implanted with ICM which has the capability of PVC detection using the implemented device PVC algorithm were analyzed from the de-identified Electronic Health Record (EHR) database linked with ICM device data warehouse. Examples of long-term PVC burden trends showing dynamic burden changes were evaluated and other PVC burden metrics such as maximum PVC burden, mean, and median PVC burden are analyzed from these ICM patients. Results PVC burden data from 1919 unique patients with implanted ICM were analyzed. 1814 patients with at least 90 days of available PVC burden were chosen for evaluation. There were 396,033 days with daily PVC burden data points that were evaluated with an average of 218 (SD=72) days with available PVC burden data per patient. The mean PVC burden which was defined as total PVC count divided by total days with ICM PVC detection enabled was 0.8 (SD=2.3) and median PVC burden was 0.02 (IQR 0-0.6). There were 6945 days (1.8%) with PVC burden values ≥10% in 168 unique patients (9.3%). 786 patients (43%) had a maximum daily PVC burden of ≤5% and 155 patients (9%) had maximum daily PVC burden between 6-10%. 107 patients (6%) had a maximum daily PVC burden between 11-20% and 40 patients (2%) had a maximum daily PVC burden &amp;gt;20%. The clinical history comparison of 1814 ICM patients based on a cutoff of a maximum daily PVC burden of 10% is shown in figure 1. Figure 2 shows examples of long-term daily PVC burden(%) trends from four different patients from this dataset showing dynamic PVC burden variabilities that only long-term monitoring of PVCs could detect. Conclusion PVC burden monitoring performed utilizing a unique PVC detection algorithm can provide longitudinal and long-term dynamic PVC burden trends in patients implanted with ICM. Dynamic changes in PVC burden may be associated with cardiac pro-arrhythmia or hospitalizations and requires further investigation.

Global burden of myocarditis from 1990 to 2019 and projections until 2030

Abstract Background Myocarditis remains a major public health challenge worldwide, which might be increasing with the pandemic of coronavirus disease 2019. Purpose This study aimed to examine the myocarditis burden at the global level, and predict the future trend until 2030. Methods Incident cases, deaths, disability-adjusted life years (DALYs), and their corresponding age-standardized rates, as metrics of myocarditis burden, were obtained from the Global Burden of Disease Study 2019. The estimated annual percentage changes (EAPCs) were calculated to reveal temporal trends from 1990 to 2019. Bayesian age-period-cohort model was used to make projections. Results Increases were noted in incident cases (62.19%) and deaths (65.4%) of myocarditis, with a slight decrease of DALYs (-0.42%). Age-standardized death rate (ASDR) showed a stable trend over time [EAPC: -0.09, 95% confidence interval (CI): -0.38 to 0.2], decreases were noted in age-standardized incidence rate (ASIR) (EAPC: -0.23, 95% CI: -0.26 to -0.21) and age-standardized DALY rate (EAPC: -1.19, 95% CI: -1.33 to -1.04). Males bore more myocarditis burden than females. Almost a third (29.94%) of myocarditis patients resided in countries with a middle sociodemographic index (SDI). Higher ASIRs were observed in regions with higher SDI levels. People aged less than 20 years in low and low-middle SDI quintiles developed myocarditis and died from it earlier than those in other quintiles. Global ASIR and ASDR were predicted to continuously decrease until 2030. Conclusion These findings suggested considerable heterogeneity in the epidemiologic patterns of myocarditis, guiding the policymakers to formulate optimal strategies and resource allocation for myocarditis.Abstract Picture 1

Abstract 13890: Global Burden of Myocarditis From 1990 to 2019 and Projections Until 2030

Introduction: Myocarditis remains a major public health challenge worldwide, which might be increasing with the pandemic of coronavirus disease 2019. This study aimed to examine the myocarditis burden at the global level, and predict the future trend until 2030. Methods: Incident cases, deaths, disability-adjusted life years (DALYs), and their corresponding age-standardized rates, as metrics of myocarditis burden, were obtained from the Global Burden of Disease Study 2019. The estimated annual percentage changes (EAPCs) were calculated to reveal temporal trends from 1990 to 2019. Bayesian age-period-cohort model was used to make projections. Results: Increases were noted in incident cases (62.19%) and deaths (65.4%) of myocarditis, with a slight decrease of DALYs (-0.42%). Age-standardized death rate (ASDR) showed a stable trend over time [EAPC: -0.09, 95% confidence interval (CI): -0.38 to 0.2], decreases were noted in age-standardized incidence rate (ASIR) (EAPC: -0.23, 95% CI: -0.26 to -0.21) and age-standardized DALY rate (EAPC: -1.19, 95% CI: -1.33 to -1.04). Males bore more myocarditis burden than females. Almost a third (29.94%) of myocarditis patients resided in countries with a middle sociodemographic index (SDI). Higher ASIRs were observed in regions with higher SDI levels. People aged less than 20 years in low and low-middle SDI quintiles developed myocarditis and died from it earlier than those in other quintiles. Global ASIR and ASDR were predicted to continuously decrease until 2030. Conclusions: These findings suggested considerable heterogeneity in the epidemiologic patterns of myocarditis, guiding the policymakers to formulate optimal strategies and resource allocation for myocarditis.