Citations

e16419 Background: Pancreatic cancer remains one of the most lethal malignancies worldwide. While high-income regions have long faced higher rates, recent trends show that lower-income regions are also beginning to see an increase. This study explores how pancreatic cancer incidence and prevalence have changed over the past 30 years among adults aged 70 and older assessing regional differences. Methods: We analyzed data from the Global Burden of Disease (GBD) spanning three decades (1990–2021) to assess pancreatic cancer incidence and prevalence rates among adults aged 70+. Data focused on different regions worldwide, grouping them by income levels using the Socio-demographic Index (SDI) and annual changes in incidence and prevalence rates were calculated. Results: In 2021, High-income Asia Pacific had the highest incidence rate at 119.52 per 100,000, whereas Low SDI regions had the lowest at 12.01 per 100,000. High-income regions accounted for the majority of cases, with over 140,000 reported, compared to fewer than 3,000 in the lowest-income areas. Andean Latin America experienced significant APC fluctuations, with a sharp rise from 2015 to 2019 followed by a decline, while High-income North America saw a recent decrease in incidence. Overall, most regions exhibit a steady increase in pancreatic cancer prevalence, with higher AAPCs in Sub-Saharan Africa, North Africa, and parts of Asia, while high-income regions show more moderate increases. Trend analysis reveals significant trends in pancreatic cancer incidence and prevalence among individuals aged 70+. Western Sub-Saharan Africa has the highest Average Annual Percent Change (AAPC) at 2.3248%, indicating the most substantial increase in prevalence from 1990 to 2021, followed by North Africa and the Middle East at 1.9906%. Low-middle SDI regions also show a steady rise with an AAPC of 1.718%, while high-income regions like High-income Asia Pacific report a notable AAPC of 1.595%. Conclusions: Our findings show a concerning rise in pancreatic cancer among older adults, with the most dramatic increases in regions like Western Sub-Saharan Africa and North Africa. To tackle this growing challenge, we need focused efforts on prevention, early detection, and accessible care, especially in lower-resource settings. Incidence percent changes. Metric Region 1990 2021 AAPC (1990-2021) Highest incidence percent change Western Sub-Saharan Africa 7.62 15.38 2.31 North Africa and Middle East 20.97 37.23 1.91 Lowest incidence percent change Caribbean 41.51 41.36 -0.016 Southern Latin America 74.05 73.89 0.006 Highest prevalence percent change Western Sub-Saharan Africa 4.54 9.21 2.32 North Africa and Middle East 12.49 22.77 1.99 Lowest prevalence rate percent change Caribbean 25.02 25.38 0.02 Southern Latin America 44.78 45.45 0.06

e16418 Background: Pancreatic cancer remains one of the most fatal malignancies globally, posing a significant burden on older populations. Despite numerous reports on its prevalence, a detailed comparative analysis of national trends among adults aged 70 and older from 1990 to 2021 is scarce. This study seeks to bridge this gap by evaluating prevalence rates using data from the Global Burden of Disease (GBD) study. Methods: Prevalence data for pancreatic cancer in individuals aged 70 years and older were obtained from the GBD-2021 dataset, encompassing 204 countries and territories for the years 1990 and 2021. The Estimated Annual Percent Change (EAPC) and corresponding 95% confidence intervals (CI) were calculated to assess trends over the period from 1990 to 2021. Results: The prevalence of pancreatic cancer has shown a significant increase since 1990, reaching its highest levels in 2021. In 1990, the United States of America (USA) reported the highest prevalence, followed by Japan and China. However, by 2021, Japan ranked first in prevalence, followed by China and the USA. The analysis revealed that in 1990, the highest prevalence rates of pancreatic cancer were observed in Greenland (91.04 per 100,000), followed by Finland (82.57 per 100,000) and Japan (76.30 per 100,000). By 2021, Japan reported the highest prevalence (126.73 per 100,000), followed by Finland (119.20 per 100,000) and Canada (109.22 per 100,000). Despite the observed prevalence rates from 1990 to 2021, Turkmenistan exhibited the most significant increase (EAPC: 15.41, 95% CI: 10.91, 21.41), followed by the Republic of Cabo Verde (EAPC: 13.61, 95% CI: 8.67, 19.59) and Mongolia (EAPC: 4.81, 95% CI: 3.11, 7.20). In contrast, the most significant declines were recorded in the Republic of San Marino (EAPC: -0.308, 95% CI: -0.51, -0.03), followed by Guam (EAPC: -0.24, 95% CI: -0.37, -0.08) and Cuba (EAPC: -0.21, 95% CI: -0.33, -0.09). Conclusions: The prevalence of pancreatic cancer among adults aged 70 and older has increased significantly over the past three decades, with distinct regional patterns. Countries like Japan, China, and the USA continue to report the highest prevalence rates. These findings highlight the urgent need for targeted prevention, screening, and treatment strategies, particularly in high-burden regions, to mitigate the growing impact of pancreatic cancer in aging populations. Prevalence percent changes. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) Highest prevalence percent change Turkmenistan 0.62 10.16 15.41 (10.91, 21.41) Republic of Cabo Verde 3.23 47.18 13.61 (8.67, 19.59) Mongolia 5.25 30.53 4.81 (3.11, 7.20) Lowest prevalence percent change Republic of San Marino 52.61 36.36 -0.308 (-0.51, -0.03) Guam 16.96 12.87 -0.24 (-0.37, -0.08) Cuba 32.65 25.52 -0.21 (-0.33, -0.09)

e22572 Background: Pancreatic cancer is a highly lethal malignancy that disproportionately impacts older populations, contributing significantly to global disease burden. Disability-adjusted life years (DALY) serve as a comprehensive metric to quantify the combined impact of mortality and morbidity. This analysis of the Global Burden of Disease Study-2021 (GBD-2021) aims to characterize trends in DALY rates attributable to pancreatic cancer among individuals aged 70 years and older across 204 nations. Methods: Data on DALY associated with pancreatic cancer for individuals aged 70+ were extracted for 204 nations from the GBD-2021 study for the years 1990 and 2021. Estimated annual percent change (EAPC) with 95% confidence intervals (CI) were calculated from 1990 to 2021. Results: The DALY rates were accessed among individuals aged 75 and older diagnosed with pancreatic cancer. In 1990, Greenland exhibited the highest DALY rate globally (2825.65), but by 2021, this position was surpassed by the United Arab Emirates (2775.52), with Greenland declining to the second-highest rate (2082.43). On the other hand, Turkmenistan had the lowest DALY rates in 1990, but by 2021, Mozambique had taken this position, with Turkmenistan ranking 170th. Despite the observed DALY rates from 1990 to 2021, Turkmenistan experienced the highest change (EAPC: 15.23, 95% CI: 10.88–21.18), followed by the Republic of Cabo Verde (EAPC: 12.88, 95% CI: 8.14–18.75) and Mongolia (EAPC: 4.53, 95% CI: 2.90–6.88). A decrease in DALY was observed in over 24 nations, with the Republic of San Marino recording the largest decline (EAPC: -0.37, 95% CI: -0.55, -0.12), followed by Bermuda (EAPC: -0.26, 95% CI: -0.43, 0.03) and Greenland (EAPC: -0.26, 95% CI: -0.45, -0.009). Conclusions: From 1990 to 2021, DALY rates related to pancreatic cancer among individuals aged 70 and older rose worldwide, particularly in Turkmenistan, the Republic of Cabo Verde, and Mongolia. There is a pressing need for global adoption of screening programs to enable early detection and treatment of these cases. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) HIGHEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PERCENT CHANGE Turkmenistan 19.66 319.09 15.22 (10.88–21.18) Republic of Cabo Verde 98.12 1361.76 12.88 (8.14–18.75) Mongolia 172.14 952.05 4.53 (2.90–6.88) LOWEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PERCENT CHANGE Republic of San Marino 1323.96 834.01 -0.37 (-0.55, -0.12) Bermuda 1696.97 1249.11 -0.26 (-0.43, 0.03) Greenland 2825.66 2082.43 -0.26 (-0.45, -0.009)

e22570 Background: Aging into the seventh decade of life marks a pivotal shift in cancer susceptibility, with pancreatic cancer (PC) emerging as one of the most relentless threats to global health. This study utilizes three decades of Global Burden of Disease (GBD) data to unravel unprecedented insights into the prevalence and incidence of PC among adults aged 70 and older. Methods: We analyzed data from the GBD study to assess the temporal trends in the incidence and prevalence of PC from 1990 to 2021. The Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC), along with 95% confidence intervals (CI), were utilized to assess the overall trends, with statistical significance evaluated using p-values. Results: Over the past three decades, the global burden of PC has surged significantly. In 1990, the global incidence of PC stood at 45.12 per 100,000, escalating to 54.47 per 100,000 by 2021. Likewise, global prevalence increased from 30.33 per 100,000 in 1990 to 40.60 per 100,000 in 2021, with incidence rates consistently exceeding prevalence, suggesting an accelerating number of new cases of PC worldwide. The AAPC analysis revealed a significant upward trajectory in both global incidence (AAPC: 0.6085, 95% CI: 0.5801, 0.6273 p < 0.000001) and prevalence (AAPC: 0.9467, 95% CI: 0.9188, 0.9659 p < 0.000001) of PC. Following the APC analysis, several notable trends emerged. The global incidence of PC experienced its most substantial increase between 2003 and 2010 (APC: 1.0806, 95% CI: 0.9817, 1.3206 p < 0.000001), while the slowest growth in incidence occurred from 1990 to 2003 (APC: 95% CI: 0.9817, 1.3206 p = 0.000400). Conversely, the global prevalence of pancreatic cancer saw its most pronounced rise between 1998 and 2001 (APC: 2.0389, 95% CI: 1.2005, 2.1962 p < 0.000001), with the slowest increase occurring from 1994 to 1998 (APC: 0.4632, 95% CI: 0.2544, 1.9767 p = 0.001200). Conclusions: The persistent rise in both incidence and prevalence of PC over the past three decades underscores a critical global health challenge, with a marked acceleration in recent years. These findings highlight the urgent need for targeted interventions and a deeper understanding of the factors driving this expanding burden, particularly as the incidence consistently outpaces prevalence. Metric Overall 1990 2021 AAPC with 95% CI (1990-2021) INCIDENCE RATES PER 100,000 Global Incidence 45.12 54.47 0.61 (0.58, 0.63) PREVALENCE RATES PER 100,000 Global Prevalence 30.33 40.60 0.95 (0.92, 0.97)

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Background As the population continues to age, the number of adults receiving care for hydrocephalus is expected to increase. Here, we assess trends in the utilization and physician reimbursement for ventriculoperitoneal shunts (VPS), lumboperitoneal shunting (LPS), and endoscopic third ventriculostomy (ETV) for adult hydrocephalus. Methods The Medicare Part B National Summary Data files from 2000 to 2021 were collected, and information was extracted on procedures performed per year, total charges billed, and actual payments. Linear mixed-model regression analyses were conducted to assess the significance of changes in procedural volume and physician reimbursement over time while adjusting for inflation. Results Over the period studied, there was a 26% increase in VPS placement (P = 0.11), 11.34% increase in ETV utilization (P < 0.01), and 43.1% decrease in LPS utilization (P < 0.01). This corresponded to annualized changes of + 4.29% for ETV procedures, −8.78% for LPS, and + 45.8% for VPS. There was a statistically significant difference in the change of rate of number of procedures annually between LPS and VPS (P = 0.04). In both inflation-unadjusted and inflation-adjusted analyses, all procedures experienced an annual decline in reimbursement with inflation-adjusted changes of −11.54%/year for ETV, −4.13% for LPS, and −13.12% for VPS. There was a statistically significant difference in the change of rate of reimbursement between LPS procedures and both ETV (P < 0.01) and VPS (P < 0.01). Conclusion Medicare reimbursement data shows that a commensurate decline in physician reimbursement has accompanied the ongoing rise in adult hydrocephalus procedures.

Background: Sarcoidosis is a multisystem disorder characterized by non-caseating granulomas in various organs. While cardiac sarcoidosis (CS) is clinically rare, it has significant implications, including heart failure, ventricular arrhythmias, and sudden cardiac death. Speckle-tracking echocardiography has emerged as a promising tool for detecting subclinical myocardial dysfunction, which is cost-efficient and readily available. This meta-analysis aims to evaluate differences in functional echocardiographic parameters between patients with CS and extracardiac sarcoidosis (ECS) to improve early recognition and management. Methods: A comprehensive search of major bibliographic databases was conducted to identify studies up to December 2024. Mean differences (MDs) with 95% CIs were pooled using the inverse-variance random-effect model. Results: Seven studies with 478 patients with sarcoidosis (CS: 159 and ECS: 319) were included. Patients with CS had a significant reduction in left ventricular global longitudinal strain (MD: −2.73; 95% CI: −4.09, −1.38; p < 0.0001) and tricuspid annular plane systolic excursion (MD: −0.59; 95% CI: −1.12, −0.05; p = 0.03) compared to patients with ECS. No significant differences in the LV global circumferential strain, interventricular septum thickness, left ventricular ejection fraction, E/A ratio, E/E’ ratio, LV end-diastolic diameter, and LV end-systolic diameter were noted. Conclusions: LV GLS and TAPSE are promising parameters for the early detection of cardiac involvement in sarcoidosis, with significant prognostic implications. Although STE provides a cost-effective and accessible alternative to CMR and FDG-PET, further research is needed to standardize its use and validate diagnostic cut-offs.

Importance Eligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings. Objective To summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine. Evidence Review A systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor ( The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine ) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate. Findings In total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria. Conclusions and Relevance Most exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.