Background: Parkinson’s disease and dementia are major neurodegenerative disorders that substantially contribute to disability, dependency, and mortality worldwide. Although prior CDC WONDER studies have separately evaluated Parkinson’s disease and dementia mortality trends, fewer analyses have examined national mortality patterns in which both conditions are recorded on death certificates simultaneously over extended time periods. Methods: We analyzed U.S. death certificates from 1999 through 2025 using the CDC WONDER Multiple Cause of Death database, identifying deaths among adults aged ≥45 years in which both Parkinson’s disease (ICD-10 G20) and dementia-related codes (F01, F03, G30, G31) were recorded anywhere on the certificate. This operational definition captures co-recorded diagnoses and does not identify clinically confirmed Parkinson’s disease dementia. Age-adjusted mortality rates (AAMRs) per 100,000 were standardized to the 2000 U.S. standard population, a method that controls for shifts in population age structure over time and allows valid temporal comparisons independent of absolute population growth. Joinpoint regression was used to quantify trends. Sensitivity analyses excluded 2025 provisional data and the COVID-19 period (1999–2019). Results: A total of 337,721 deaths were identified. Overall AAMR increased from 5.75 (95% CI: 5.60–5.90) in 1999 to 11.15 (95% CI: 10.98–11.32) in 2025 (AAPC: 2.07; p = 0.002). A sharp transient increase occurred in 2020, attributable to pandemic-related factors including disproportionate COVID-19 mortality among older adults with neurodegenerative conditions, care disruptions, and changes in death-certificate coding practices. Following this pandemic-era peak, AAMRs declined significantly through 2025 and should be interpreted cautiously given provisional data. Males (AAPC: 2.14), non-Hispanic White individuals (AAPC: 2.29), the Midwest region (AAPC: 2.65), and non-metropolitan areas carried the highest mortality burden. Mortality was greatest among adults aged ≥85 years. Conclusion: Population-level death rates involving co-recorded Parkinson’s disease and dementia demonstrated significant temporal changes over the study period, with marked demographic and geographic disparities. These findings reflect death-certificate surveillance data and cannot establish clinical co-occurrence, causal relationships, or individual disease risk.

Meningitis remains a significant cause of morbidity and mortality in the United States despite advances in vaccination, antimicrobial therapy, and critical care. However, long-term national mortality patterns across demographic and geographic subgroups remain incompletely characterized. This study evaluated temporal trends in meningitis-associated mortality among U.S. adults aged ≥25 years from 1999 to 2024 using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death database. Death certificates listing meningitis as either the underlying cause or a contributing cause of death were identified using ICD-10 codes to capture meningitis-associated mortality. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Across the study period, meningitis-associated mortality demonstrated an early decline followed by stabilization and more recent increases in several subgroups. AAMRs decreased significantly from 1999 to 2001 (APC: −14.09%; p = 0.0029) and from 2001 to 2013 (APC: −4.74%; p < 0.000001), followed by a significant increase from 2013 to 2024 (APC: 1.78%; p = 0.0059). Despite these later increases, the overall AAPC across the full study period remained significantly negative (AAPC: −2.73%; p < 0.000001). Earlier analyses using shorter observation windows did not demonstrate a statistically significant overall trend; the significance observed in the present analysis reflects the inclusion of extended mortality data through 2024. Mortality rates were consistently higher among males and adults aged ≥65 years. Non-Hispanic Black individuals experienced increasing mortality after 2013, while Hispanic individuals demonstrated a sustained increase across the entire study period. Regional analyses showed recent increases in the Northeast, South, and West, while non-metropolitan areas did not experience statistically significant improvement through 2020. In summary, meningitis-associated mortality among U.S. adults declined significantly during the early study years but has shown stabilization and recent increases in several demographic and geographic subgroups since approximately 2013. Although overall mortality across the full study period remains lower than baseline levels, these emerging disparities highlight the importance of continued surveillance and targeted public health interventions.

Background: Cardiovascular disease (CVD) and cancer share common risk factors, and cancer survivors experience elevated long-term cardiotoxicity. Traditional risk-based metrics require person-time denominators that are unavailable in aggregate public health databases. This study introduces a proportional co-listing framework to detect population-level cardiovascular surveillance signals on death certificates across cancer types and demographic strata. Methods: We conducted a national cross-sectional surveillance analysis using CDC WONDER Multiple Cause-of-Death data from 1999 to 2020 for decedents aged ≥ 15 years. Utilizing an “any-mention” framework, we calculated the Proportional Mortality Ratio (PMR), defined as the ratio of CVD co-listing on cancer-related death certificates to CVD listing on non-cancer certificates. Temporal trends were evaluated using joinpoint regression to estimate the average annual percent change (AAPC). Analyses were stratified by age, sex, race/ethnicity, geography, and index cancer subtypes (lung, colon, and leukaemia). Results: Of 56,014,102 death certificates analyzed, 13,917,133 (24.8%) listed a malignant neoplasm, of which 3,997,238 (28.7%) co-listed CVD. Across the lifespan, the overall PMR followed a reverse J-shaped curve. Proportional co-listing was highest in the youngest cohort (ages 15–24: PMR 1.828, 95% CI: 1.778–1.879), declined to a nadir at ages 55–64 (PMR 0.336, 95% CI: 0.335–0.337), and rose modestly in older adulthood. From 1999 to 2020, PMRs increased significantly across all adult age groups, peaking at ages 55–64 (AAPC 1.69%, 95% CI: 1.52–1.83, p < 0.001). Young-adult PMR elevations were consistently higher in male, metropolitan, and Hispanic/Latino decedents. Among subtypes, leukaemia demonstrated the highest relative CVD co-listing in young adults (PMR 2.174), whereas colon cancer showed no statistically significant elevation (PMR 1.173, 95% CI: 0.951–1.447). Conclusions: Cardiovascular co-listing on US cancer death certificates is highly patterned by age, demographics, and cancer subtype. While elevated PMRs in young adults are consistent with patterns previously reported in cardio-oncology literature, sub-unity PMRs in middle-aged and older adults may reflect under-documentation of cardiovascular comorbidities in oncology settings alongside denominator effects arising from frequent CVD listing on non-cancer certificates. Improving comorbidity documentation on death certificates may enhance the utility of national administrative data for cardio-oncology surveillance and research.

Background: Abdominal aortic aneurysm (AAA) remains an important cause of cardiovascular mortality in the United States despite advances in screening, surveillance, and aneurysm repair. Contemporary national analyses evaluating long-term AAA mortality trends across demographic and geographic subgroups remain limited, particularly following the COVID-19 pandemic period. Objective: To evaluate temporal trends in AAA-related mortality among U.S. adults aged ≥ 65 years from 1999 to 2024 and characterize demographic and geographic disparities. Methods: A retrospective population-based study was conducted using the CDC WONDER Multiple Cause of Death database. AAA-related deaths were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes I71.3 and I71.4. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population. Mortality trends were stratified by sex, age, race/ethnicity, census region, and urbanization status. Joinpoint regression analysis was used to estimate annual percent change (APC) and average annual percent change (AAPC). Results: Between 1999 and 2024, a total of 208,476 AAA-related deaths among U.S. adults aged ≥ 65 years were recorded. Overall AAMR declined significantly from 32.61 per 100,000 population in 1999 to 12.17 per 100,000 population in 2024 (AAPC −3.86%; 95% confidence interval [CI]: −4.43 to −3.30; p < 0.001). Mortality rates remained consistently higher among males, adults aged ≥ 85 years, non-Hispanic White individuals, residents of the Midwest, and non-metropolitan populations. Joinpoint analysis demonstrated sustained declines across most demographic groups. Although several subgroups exhibited a temporary plateau in declining mortality trends during the pandemic era, these trend changes did not reach statistical significance. Following 2021, mortality rates resumed a significant downward trend. Conclusions: AAA-related mortality among U.S. adults aged ≥ 65 years declined substantially between 1999 and 2024; however, important demographic and geographic disparities persist. Continued efforts aimed at risk factor reduction, equitable screening access, and preventive vascular care remain essential to further reduce AAA-related mortality among older adults.

Background: Despite three decades of neuroprotective failures in acute ischaemic stroke (AIS), edaravone dexborneol (EDB) achieved regulatory approval in China by demonstrating superiority over edaravone monotherapy. The only prior meta-analysis evaluated a single functional endpoint, excluded four subsequent studies including the pivotal TASTE-2 trial, and performed no comparator stratified analyses leaving the totality of evidence uncharacterised. Methods: A PROSPERO registered systematic review and meta-analysis searched PubMed, Embase, Scopus, clinical trials.gov and Cochrane through May 2026. Eligible studies were randomised controlled trials and comparative observational studies of EDB in adult AIS patients. Co-primary outcomes were 90-day excellent functional recovery (mRS 0–1) and functional independence (mRS 0–2). Random effects meta-analysis, GRADE certainty rating, and Trial Sequential Analysis (TSA) were applied throughout. Results: Eleven studies enrolling 4706 patients seven RCTs and four comparative observational studies were included. EDB significantly improved mRS 0–1 (RR 1.14, 95% CI 1.08–1.20; p < 0.00001; I ² = 0%; 9 studies; n = 4,474; GRADE: HIGH) and mRS 0–2 (RR 1.08, 95% CI 1.03–1.13; p = 0.001; I ² = 1%; 8 studies; n = 4089; GRADE: HIGH). TSA showed that accrued information exceeded the required information size for both endpoints (555.4% for mRS 0–1; 505.3% for mRS 0–2), and the O’Brien–Fleming benefit boundary was crossed for mRS 0–1 (Z = 4.70), confirming evidentiary sufficiency for this endpoint. For mRS 0–2, the required information size was reached within the earliest contributing trial, so the sequential boundary could be assessed only at the first information fraction, where it was not crossed (Z = 1.56); TSA-based sufficiency is therefore not claimed for mRS 0–2. Ninety day mortality was non-significantly reduced (RR 0.87, 95% CI 0.67–1.13; GRADE: MODERATE), with only 32.4% of the required information size accrued. Adverse event rates were equivalent (RR 1.01); symptomatic intracranial haemorrhage was numerically lower with EDB (RR 0.73, 95% CI 0.49–1.07). All seven RCTs carried a low risk of bias, indicating a consistently high methodological quality across the included evidence base. Conclusion: EDB produces a TSA-confirmed improvement in 90-day excellent functional recovery (mRS 0–1). For functional independence (mRS 0–2), the pooled effect was significant with GRADE HIGH certainty, but TSA could not confirm evidentiary sufficiency because the sequential boundary was assessable only at the earliest information fraction, where it was not crossed, so further corroboration is warranted; a reassuring though not fully conclusive safety profile was observed; certainty for mortality and several secondary and safety outcomes remains lower and is detailed below. Definitive inference on mortality requires blinded, adequately powered, multinational trials.