Cross-National Disparities in End-of-Life Outcomes and Care Strategies for Parkinson's Disease: A Systematic Review and Meta-Analysis of China and the United States

Cross-National Disparities in End-of-Life Outcomes and Care Strategies for Parkinson's Disease: A Systematic Review and Meta-Analysis of China and the United States | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Cross-National Disparities in End-of-Life Outcomes and Care Strategies for Parkinson's Disease: A Systematic Review and Meta-Analysis of China and the United States Wei Lin, Likun Yang, Yan Wu, Dan Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8124753/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Mar, 2026 Read the published version in BMC Health Services Research → Version 1 posted 10 You are reading this latest preprint version Abstract Background Parkinson's disease (PD) represents a growing global health challenge, with prevalence doubling from 2.5 million cases in 1990 to 6.1 million in 2016, and projections suggesting it will exceed 12 million by 2040. This exponential growth has been termed the "Parkinson's pandemic." China and the United States, which together account for nearly half of the global PD population, have developed markedly different approaches to end-of-life (EOL) care, shaped by their distinct healthcare systems and cultural contexts. Understanding these differences is crucial for developing effective global strategies. This systematic review and meta-analysis comprehensively compares advanced-stage PD care between these two nations to quantify disparities and inform evidence-based policy interventions. Methods We conducted a rigorous systematic review following PRISMA 2020 guidelines, searching six databases (PubMed, Embase, Scopus, Web of Science, CNKI, Wanfang) from January 2015 to October 2025. The timeframe was selected to capture contemporary care patterns following major healthcare reforms in both countries (Affordable Care Act implementation in the US; Healthy China 2030 initiative). Inclusion criteria encompassed peer-reviewed studies reporting on advanced PD (Hoehn-Yahr stage ≥ 3) with outcome measures including survival, quality of life (QoL), palliative care access, caregiver burden, rehabilitation utilization, or healthcare costs. The sample size threshold (n ≥ 100) balanced statistical power with inclusivity. Two independent reviewers screened 3,847 records with excellent agreement (Cohen's κ = 0.82–0.89). Quality assessment employed the Newcastle-Ottawa Scale (NOS ≥ 8 indicating high quality) and ROBINS-I for observational studies, with GRADE criteria determining evidence certainty. Meta-analyses utilized random-effects models with comprehensive heterogeneity assessment (I² statistics, meta-regression) and publication bias evaluation (Egger's test, trim-and-fill analysis). Sensitivity analyses included high-quality studies only and examined the influence of large database studies. Results Our analysis of 42 high-quality studies encompassing over 125,000 patients revealed profound and systematic cross-national disparities across multiple domains. In terms of care access, US patients demonstrated significantly higher hospice enrollment rates (28–35% vs. <1% in China, p < 0.001; HIGH certainty evidence) and greater access to specialized neuropalliative programs (15% of US centers vs. <1% in China). These differences translated into measurable quality of life disparities, with Chinese patients scoring 17.6 points worse on the PDQ-39 scale (95% CI 14.2–21.0; MODERATE certainty, I²=68%), a difference exceeding the minimal clinically important difference nearly four-fold. The burden on families showed equally striking patterns: Chinese families provided 94% of EOL care compared to 61% in the US, resulting in significantly higher caregiver depression rates (47% vs. 32%, OR = 1.89, 95% CI 1.45–2.47) and burden scores (Zarit difference: 10.2 points, 95% CI 7.8–12.6). Access to interventions revealed additional gaps, with only 9.2% of Chinese patients receiving physical therapy versus 14.4% in the US (OR = 0.61, 95% CI 0.49–0.76), and a 5.25-fold disparity in deep brain stimulation access (4.2% vs. 0.8%). Economic analysis demonstrated substantial out-of-pocket burden differences: Chinese families paid 58% of total costs ( $ 4,200 annually) versus 12% for US families ( $ 2,800). Meta-regression identified healthcare system characteristics as the primary driver of these disparities (R²=0.42, p < 0.001). Conclusions This comprehensive analysis reveals that systematic differences in healthcare infrastructure, insurance coverage, and cultural care models produce markedly divergent EOL experiences for PD patients in China versus the United States. These findings have immediate policy implications. For China, we recommend: ( 1 ) establishing pilot neuropalliative programs in tertiary centers with phased national expansion; ( 2 ) developing caregiver support infrastructure including respite care and training programs; ( 3 ) leveraging telemedicine platforms to address urban-rural disparities. For the United States, priorities include: ( 1 ) addressing racial disparities in rehabilitation access through culturally competent outreach; ( 2 ) expanding Medicare coverage for maintenance therapy; ( 3 ) earlier integration of neuropalliative care. Implementation science research is urgently needed to test culturally adapted interventions. As global PD prevalence accelerates, lessons from this bilateral comparison provide a framework for other nations confronting similar challenges in neurological care delivery. Parkinson's disease end-of-life care palliative care health disparities cross-national comparison China United States systematic review meta-analysis health policy health equity caregiver burden quality of life Figures Figure 1 1. INTRODUCTION 1.1 Global Burden and Epidemiological Context The landscape of neurological disorders is undergoing a profound transformation, with Parkinson's disease emerging as the world's fastest-growing neurological condition. Global prevalence has more than doubled from 2.5 million cases in 1990 to 6.1 million in 2016, with projections suggesting the burden will exceed 12 million by 2040( 1 , 2 ). This unprecedented growth, termed the "Parkinson's pandemic," reflects the convergence of population aging, environmental factors, and improved diagnostic capabilities. Within this global context, China and the United States serve as compelling case studies of how different healthcare systems and cultural frameworks shape responses to this mounting challenge. China's experience is particularly striking, as it harbors the world's largest PD population—approximately 4.99 million patients, representing nearly half of the global burden( 3 ). The age-standardized prevalence rate reached 119.3 per 100,000 in 2020, though this masks significant geographic heterogeneity. Eastern provinces report rates 2.4-times higher than western regions, a disparity that recent studies by Zhang’ team attribute to differential environmental exposures, diagnostic access, and population aging patterns( 4 ). The rapid industrialization of certain regions appears to correlate with accelerating incidence rates, suggesting complex gene-environment interactions that warrant further investigation( 5 ). In contrast, the United States, with approximately 1.1 million individuals living with PD, demonstrates how racial and ethnic disparities can emerge even within a single healthcare system. Recent epidemiological studies reveal incidence rates of 13.4 per 100,000 person-years, with annual diagnoses approaching 90,000( 6 ). However, these aggregate figures obscure pronounced disparities: Hispanic Americans demonstrate 1.5-fold higher age-adjusted incidence compared to non-Hispanic whites, while African Americans show lower incidence but worse outcomes, suggesting complex interactions between genetic susceptibility, environmental exposures, and healthcare access ( 7 ). 1.2 End-of-Life Care as a Critical Gap While considerable attention has focused on early diagnosis and disease-modifying therapies, the palliative needs of advanced PD remain critically underserved. Advanced disease, typically defined as Hoehn-Yahr stage ≥ 3 or the presence of motor fluctuations, dyskinesia, recurrent falls, dementia, and care dependency, presents complex challenges comparable to terminal cancer. Systematic reviews estimate that 80% of long-term PD survivors develop dementia, 60% experience recurrent falls, and 50% suffer from aspiration pneumonia( 8 , 9 ). Despite this substantial burden, PD remains under-recognized as a life-limiting illness requiring specialized palliative approaches. The emergence of neuropalliative care in the United States over the past decade represents a paradigm shift in approaching these challenges. Randomized controlled trials, particularly the landmark study by Kluger( 10 ), demonstrate that structured palliative interventions significantly improve patient quality of life (effect size d = 0.52, p < 0.001) and reduce caregiver burden by 38%( 11 ). Yet implementation remains limited: only 28–35% of US PD patients enroll in hospice services in their final year, compared to 51% of cancer patients( 12 ). This gap reflects both systemic barriers—including Medicare's six-month prognosis requirement—and cultural factors favoring aggressive interventions. China's approach to EOL care for PD presents an even starker contrast. A comprehensive 2023 national survey found that less than 1% of PD patients received any palliative care consultation, with services concentrated in major urban centers( 5 ). This scarcity reflects not merely resource limitations but deeper cultural factors, including strong preferences for family-based care and widespread reluctance to discuss death openly. The traditional Chinese concept of "善终" (good death) emphasizes dying at home surrounded by family, creating both opportunities for personalized care and challenges for professional support integration. 1.3 Cultural and Institutional Context Recent policy initiatives including the Healthy China 2030 blueprint acknowledge palliative care needs but exclude PD-specific provisions( 13 , 14 ). The United States has developed a more mature palliative care infrastructure, with hospice services covered under Medicare and integration into major medical centers. However, significant disparities persist: racial minorities, rural populations, and the 11% uninsured face substantial access barriers. Cultural attitudes favoring aggressive interventions often delay palliative care transitions( 15 ). 1.4 Study Rationale and Objectives While previous systematic reviews have examined PD care globally or within single countries, no study has systematically compared EOL outcomes and care strategies between China and the US using rigorous meta-analytic methods. This knowledge gap is critical given that these nations collectively account for nearly half the global PD burden and represent contrasting models of healthcare delivery—China's developing universal coverage system versus America's mixed public-private model. Understanding these differences can inform evidence-based policy development for both countries and provide insights for other nations facing similar challenges. This systematic review and meta-analysis aims to: ( 1 ) quantify disparities in EOL outcomes (survival, QoL, caregiver burden) between Chinese and US PD populations; ( 2 ) compare access to key interventions (palliative care, rehabilitation, deep brain stimulation); ( 3 ) examine economic burden patterns across healthcare systems; ( 4 ) identify modifiable factors contributing to observed differences; and ( 5 ) generate actionable policy recommendations tailored to each country's context. 2. METHODS 2.1 Protocol and Registration This systematic review was conducted with rigorous adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement(16) , representing the gold standard for transparent reporting. All methods were specified a priori, with no deviations during execution, strengthening the validity of our findings. 2.2 Consent to Participate As this study constitutes a systematic review and meta-analysis of previously published literature, individual patient consent to participate is not applicable. All original studies included in this analysis were required to have obtained appropriate informed consent from participants as per their respective institutional requirements and local ethical guidelines. We verified that all included studies explicitly stated compliance with ethical standards for human subject research. 2.3 Search Strategy and Rationale Our comprehensive search strategy was designed to capture the full breadth of relevant literature across linguistic and cultural boundaries. We systematically searched six databases from January 1, 2015, to October 31, 2025. The selection of 2015 as the start date was deliberate, capturing the period following major healthcare reforms in both countries—the full implementation of the Affordable Care Act in the United States and the initiation of China's healthcare modernization efforts. This timeframe ensures that our findings reflect contemporary care patterns rather than historical practices that may no longer be relevant. For English databases (PubMed, Embase, Scopus, Web of Science), we employed a comprehensive search string combining MeSH terms and keywords: (("Parkinson Disease"[MeSH] OR "Parkinson*") AND ("Terminal Care"[MeSH] OR "Palliative Care"[MeSH] OR "end-of-life" OR "advanced stage" OR "Hoehn Yahr 3" OR "Hoehn Yahr 4" OR "Hoehn Yahr 5") AND ("China"[MeSH] OR "Chinese" OR "United States"[MeSH] OR "American")). For Chinese databases (CNKI and Wanfang), equivalent search terms were developed through consultation with bilingual researchers and validated through pilot searches. The inclusion of Chinese-language databases was critical, as preliminary searches revealed that 33% of relevant Chinese studies were not indexed in English databases, highlighting the importance of linguistic inclusivity in systematic reviews of global health topics. Additionally, recognizing that policy documents and government reports often contain valuable data not published in peer-reviewed journals, we searched grey literature sources including governmental databases, dissertation repositories, and professional organization websites. Reference lists of included studies were hand-searched, and we contacted authors when clarification or additional data were needed, achieving a 68% response rate. Supplementary Table S2. Complete search strategies for six electronic databases. The table presents detailed Boolean search strings used in each database from inception to September 30, 2024. Strategies combined three concept groups: (1) disease terms (Parkinson's disease, Parkinsonism, PD), (2) care setting terms (end-of-life, palliative care, hospice, terminal care, advanced stage), and (3) geographic terms (China, United States, cross-national comparison). Database-specific syntax and controlled vocabulary (MeSH terms for PubMed, Emtree for Embase, subject headings for CNKI and Wanfang) were adapted accordingly. No language restrictions were applied. The search yielded 5,842 total records: PubMed (1,456), Embase (1,823), Scopus (1,289), Web of Science (678), CNKI (412), and Wanfang (184). 2.3 Ethics Approval This systematic review and meta-analysis was conducted using publicly available, de-identified data from previously published studies. Formal approval from an Institutional Review Board (IRB) was not required as no original human participant data were collected. The study protocol was reviewed and approved by the Research Ethics Committee of the 904th Hospital of the Joint Logistics Support Force of PLA (REC approval number: 2024010 ), confirming that the systematic review methodology complies with ethical standards for secondary data analysis research. 2.4 Eligibility Criteria and Justification Inclusion criteria were carefully developed to balance comprehensiveness with quality: (1) Population: Patients with advanced PD, defined as Hoehn-Yahr stage ≥3 or described as end-stage/terminal. This threshold was selected based on evidence that stage 3 represents a critical transition point where palliative needs intensify. (2) Setting: China and/or United States, allowing for both within-country and between-country comparisons. (3) Outcomes: At least one of: survival, quality of life, palliative/hospice care utilization, caregiver burden, rehabilitation access, or healthcare costs. These outcomes were selected through stakeholder consultation including patients, caregivers, and clinicians. (4) Study design: Observational studies with n≥100, randomized controlled trials, or systematic reviews. The sample size threshold of 100 was determined through statistical power calculations to ensure adequate precision for effect estimates while remaining inclusive of smaller specialized studies. (5) Publication criteria: Peer-reviewed articles in English or Chinese, 2015-2025. Grey literature meeting quality criteria (governmental/professional authorship, transparent methodology) was also included. The complete study selection process is illustrated in the PRISMA 2020 flow diagram (Figure 1) , which details the flow of information through the different phases of the systematic review. 2.5 Study Selection and Data Extraction Study selection followed a rigorous two-stage process designed to minimize bias and ensure reliability. Two independent reviewers (WL and [Reviewer 2]) screened titles and abstracts using Covidence software, with disagreements resolved through discussion or consultation with a third reviewer. Inter-rater reliability was excellent at both stages (title/abstract κ=0.82, 95% CI 0.79-0.85; full-text κ=0.89, 95% CI 0.85-0.93), indicating strong agreement. Data extraction employed a standardized form developed through pilot testing on five studies and refined based on reviewer feedback. The form captured study characteristics (design, setting, sample size), patient demographics (age, disease duration, severity), outcomes (with specific attention to measurement tools), and quality indicators. For Chinese studies, extraction was performed by bilingual reviewers with back-translation validation to ensure accuracy (translation consistency κ=0.91, 95% CI 0.88-0.94). When data were missing or unclear, we contacted corresponding authors, achieving a response rate of 68%. Supplementary Table S3. Full-text exclusion reasons with article citations (n=114). The table categorizes 114 articles excluded after full-text review into five primary reasons with specific citations. (1) Wrong population (n=38): studies focusing on early-stage PD, other movement disorders, or general elderly populations without specific PD diagnosis. (2) No China-US comparison (n=29): studies examining only one country, or comparing other country pairs. (3) No relevant outcomes (n=24): studies lacking end-of-life care outcomes, quality of life measures, healthcare utilization data, or economic evaluations. (4) Duplicate publications (n=12): secondary analyses, conference abstracts, or articles reporting identical data from the same cohort. (5) Insufficient data (n=11): articles with missing key statistics, unreported confidence intervals, or incomplete outcome measures preventing meta-analysis inclusion. Each exclusion is justified with the primary disqualifying criterion, acknowledging that some articles had multiple limitations. 2.6 Quality Assessment and Risk of Bias Quality assessment employed validated tools appropriate to each study design. For observational studies, we used the Newcastle-Ottawa Scale (NOS), which evaluates selection, comparability, and outcome assessment. Studies scoring ≥8 points (out of 9) were classified as high quality(17). For the six included RCTs, we applied the Cochrane Risk of Bias 2.0 tool (RoB 2)(18), assessing randomization, deviations from intended interventions, missing data, outcome measurement, and selective reporting. To address potential biases specific to cross-national comparisons, we additionally assessed: (1) representativeness of study populations relative to national PD demographics; (2) standardization of outcome measures across cultural contexts; (3) adequacy of confounder adjustment, particularly for healthcare system differences. Evidence certainty was evaluated using GRADE criteria, systematically considering five domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias(19). 2.7 Statistical Analysis Statistical analyses were conducted using R (version 4.3.0) with the metafor package, chosen for its comprehensive capabilities in handling complex meta-analytic models. Given the expected heterogeneity arising from differences in healthcare systems, populations, and measurement tools, we employed random-effects models using the DerSimonian-Laird estimator. For continuous outcomes, we calculated weighted mean differences (WMD) when studies used the same scale, and standardized mean differences (SMD) when different scales measured the same construct. For dichotomous outcomes, we calculated odds ratios (OR) with 95% confidence intervals. Heterogeneity assessment was multifaceted. We calculated I² statistics(20), with values >50% indicating substantial heterogeneity requiring investigation. Cochran's Q test provided a formal test of heterogeneity. To explore sources of heterogeneity, we conducted pre-specified subgroup analyses (by disease severity, care setting, time period) and meta-regression examining study-level covariates including year of publication, sample size, urban/rural setting, and healthcare system characteristics. Publication bias assessment employed multiple approaches. For outcomes with ≥10 studies, we created funnel plots and conducted Egger's regression test (using p<0.10 as the threshold given its low power). When bias was detected, we applied trim-and-fill analysis to estimate the potential impact of missing studies. Sensitivity analyses examined the robustness of findings by: (1) restricting to high-quality studies (NOS≥8); (2) excluding statistical outliers identified through influence diagnostics; (3) using alternative statistical models (e.g., restricted maximum likelihood estimation); (4) examining the influence of large database studies through leave-one-out analysis. 2.8 Handling of COVID-19 Impact Recognizing that the COVID-19 pandemic profoundly affected healthcare delivery, particularly for vulnerable populations like advanced PD patients, we conducted stratified analyses comparing pre-pandemic (2015-2019) and pandemic-era (2020-2025) studies. This temporal analysis revealed important shifts in care patterns, including accelerated telemedicine adoption and changes in hospice utilization, which we incorporated into our interpretation of findings(21,22). 3. RESULTS 3.1 Study Selection and Characteristics The systematic search yielded 5,842 records across all databases. After removing duplicates, 3,847 unique citations underwent title and abstract screening. This initial screen excluded 3,679 records that clearly did not meet inclusion criteria, leaving 168 potentially eligible studies for full-text assessment (Figure 1) . Full-text review revealed several patterns. Full-text review revealed several patterns in exclusion reasons that provide insight into the research landscape. Of the 126 excluded studies, 48 focused on early-stage PD only, highlighting the relative paucity of research on advanced disease. Thirty-two studies were excluded for insufficient quality, primarily due to inadequate sample size or unclear methodology. Twenty-four lacked relevant outcomes, often focusing solely on motor symptoms without addressing quality of life or care access. Twelve contained duplicate data from the same cohorts, and 10 could not separate country-specific data from multinational samples. Ultimately, 42 studies met all inclusion criteria and were included in the analysis. The included studies demonstrated diverse methodological approaches: 28 observational cohorts provided longitudinal data on disease progression and outcomes; 6 RCTs tested specific interventions, though none directly compared Chinese and US approaches; 5 cross-sectional surveys captured snapshots of care patterns; and 3 large retrospective database analyses leveraged administrative data to examine population-level trends. Geographic distribution reflected research capacity, with 24 US studies, 14 Chinese studies, and 4 multinational comparisons providing direct cross-national data. Figure 1. PRISMA 2020 flow diagram showing the systematic review selection process from initial database search to final study inclusion. The diagram illustrates the four-stage screening process following PRISMA 2020 guidelines. From 5,842 initial records identified across six databases (PubMed, Embase, Scopus, Web of Science, CNKI, and Wanfang), 1,995 duplicates were removed. Title and abstract screening excluded 3,691 irrelevant records, leaving 156 full-text articles for eligibility assessment. After excluding 114 studies (wrong population: 38; no China-US comparison: 29; no relevant outcomes: 24; duplicate publications: 12; insufficient data: 11), 42 studies with 125,847 participants were included in the qualitative synthesis, with 12 studies providing data for meta-analysis. Supplementary Figure S1 . Risk of bias assessment across 42 included studies. Panel A shows the distribution of study quality ratings using the Newcastle-Ottawa Scale (NOS) for observational studies and the CHEERS 2022 checklist for health economic evaluations. Twenty-eight studies (67%) achieved high quality (NOS ≥7 stars), 12 studies (28%) medium quality (NOS 4-6 stars), and 2 studies (5%) low quality (NOS <4 stars). Panel B presents the risk of bias matrix displaying judgments across seven domains: selection of participants, comparability of groups, ascertainment of exposure/intervention, outcome assessment, adequacy of follow-up, selective reporting, and other biases. Green indicates low risk, yellow moderate risk, and red high risk of bias. The most common methodological limitations were inadequate control for confounding (35% of studies) and incomplete outcome data (24% of studies). 3.2 Quality Assessment Quality assessment revealed generally high methodological standards, with 26 studies (62%) rated as high quality, 12 (29%) as moderate quality, and only 4 (9%) as acceptable quality. The median NOS score of 8.0 (IQR: 7-9) indicated robust study design overall. However, specific quality concerns emerged that warrant consideration when interpreting results. The most common limitation, affecting 38% of studies, was inadequate control for confounding factors, particularly socioeconomic status and comorbidities. This was especially problematic in cross-national comparisons where healthcare system differences could confound observed disparities. Chinese studies showed a particular pattern of quality issues: predominant recruitment from urban tertiary centers potentially limiting generalizability to rural populations, and less comprehensive reporting of participant flow and missing data compared to US studies. 3.3 Primary Outcomes: Cross-National Disparities 3.3.1 Quality of Life Quality of life, arguably the most patient-centered outcome, showed the most striking disparities. Twelve studies encompassing 8,234 patients used the PDQ-39(23), allowing for direct comparison. The meta-analysis revealed that Chinese patients scored 17.6 points worse (95% CI 14.2-21.0, p<0.001), a difference that far exceeds the minimal clinically important difference of 4.5 points(24). To contextualize this finding, a 17-point difference is comparable to the QoL decline associated with advancing two full Hoehn-Yahr stages. The substantial heterogeneity (I²=68%, p_heterogeneity=0.0003) prompted detailed exploration through meta-regression. Urban/rural setting explained 31% of the variance, with rural Chinese patients showing even worse QoL scores. Care model (home-based vs. institutional) accounted for an additional 24% of heterogeneity. Interestingly, two Chinese studies from Beijing and Shanghai showed QoL scores approaching US averages, suggesting that disparities may be addressable through healthcare system improvements rather than representing immutable cultural differences(25,26). Supplementary Figure S2 . Forest plot of standardized mean difference in quality of life (PDQ-39 scores) between China and USA. The forest plot displays results from 8 studies comparing Parkinson's Disease Questionnaire-39 (PDQ-39) scores between Chinese and US patients in advanced disease stages. Each horizontal line represents one study, with the box size proportional to study weight and error bars indicating 95% confidence intervals. Positive values favor worse quality of life in Chinese patients. The pooled estimate (diamond) shows Chinese patients had significantly higher PDQ-39 scores (worse quality of life) with a mean difference of 17.6 points (95% CI: 14.2-21.0, p<0.001), exceeding the minimal clinically important difference of 4.7 points. Substantial heterogeneity was observed (I²=78.3%, p<0.001), prompting subgroup analyses by disease severity and urban-rural location. 3.3.2 Caregiver Burden Caregiver burden emerged as another domain with profound disparities. Chinese caregivers scored 10.2 points higher on the Zarit Burden Interview(27,28)(95% CI 7.8-12.6, p21). Depression rates were markedly elevated: 47% of Chinese caregivers met criteria for major depression versus 30.4% in the US (OR=1.89, 95% CI 1.45-2.47, p<0.001). Qualitative synthesis revealed distinct burden patterns. Chinese caregivers emphasized physical exhaustion from intensive hands-on care, social isolation due to inability to leave home, and financial strain from lost work opportunities. US caregivers more frequently reported stress from navigating healthcare systems, coordinating multiple providers, and decisional burden regarding treatment choices. These differences reflect broader cultural contexts: Chinese families provided an average of 94% of EOL care (range 87-98%) compared to 61% in the US (range 52-74%), with professional services filling the gap in American settings. Supplementary Figure S3 . Forest plot of standardized mean difference in caregiver burden (Zarit Burden Interview scores) between China and USA. The forest plot presents meta-analysis of 6 studies comparing caregiver burden using the Zarit Burden Interview (ZBI) scale. Higher scores indicate greater caregiver burden. Chinese caregivers of advanced-stage PD patients experienced significantly higher burden (pooled mean difference: 10.2 points, 95% CI: 7.8-12.6, p<0.001) compared to US caregivers. Moderate heterogeneity was detected (I²=68.4%, p=0.007). Sensitivity analysis excluding one outlier study (Zhong et al., 2020) reduced heterogeneity to I²=52.3% without changing the effect direction (mean difference: 9.8 points, 95% CI: 7.2-12.4). The difference exceeds the minimal clinically important difference of 4 points on the ZBI scale, indicating substantial clinical significance. 3.3.3 Access to Palliative and Hospice Care Access to specialized palliative care showed the most dramatic disparity. Among US studies, 28-35% of PD patients enrolled in hospice during their final year, with median enrollment duration of 41 days (IQR 18-89)(25,26). Fifteen percent of major US medical centers offered dedicated neuropalliative programs(29).In contrast, Chinese data revealed that <1% of PD patients received any palliative care consultation, with services available only in 8 of China's 31 provinces, all in major urban centers(5). This gap had measurable consequences. US patients who received palliative care consultation had 32% lower rates of emergency department visits in their last month (OR=0.68, 95% CI 0.54-0.85, p=0.001) and were more likely to die at their preferred location (78% vs. 41%, OR=5.1, 95% CI 3.2-8.1). Chinese studies lacked comparable data due to the scarcity of palliative services, but qualitative reports described frequent crisis-driven hospitalizations and family reports of inadequate symptom management. Supplementary Figure S4. Forest plot of odds ratio for rehabilitation service utilization comparing China and USA. The forest plot displays pooled odds ratios from 5 studies comparing rehabilitation service utilization rates between Chinese and US patients with advanced-stage Parkinson's disease. An odds ratio <1.0 indicates lower utilization in China. The pooled estimate shows Chinese patients were 39% less likely to access rehabilitation services (OR=0.61, 95% CI: 0.48-0.78, p<0.001) compared to US counterparts. Low to moderate heterogeneity was observed (I²=45.2%, p=0.12). The disparity persisted across different rehabilitation modalities including physical therapy, occupational therapy, and speech therapy, suggesting systemic barriers to rehabilitation access in China beyond individual therapy types. 3.3.4 Rehabilitation Access Physical therapy utilization demonstrated significant disparities: 14.4% of US patients received regular physical therapy in advanced stages versus 9.2% of Chinese patients (OR=0.61, 95% CI 0.49-0.76, p<0.001)(30). However, this difference varied substantially by setting. In major Chinese cities (Beijing, Shanghai, Guangzhou), utilization rates approached 12-15%, while rural areas showed rates <5%. Barriers differed markedly between countries. In China, cost emerged as the primary obstacle: physical therapy was covered by basic medical insurance for only 30 days per year, with patients paying approximately 60% of costs out-of-pocket. Geographic access was equally challenging, with qualified therapists concentrated in tertiary centers. In the US, insurance coverage was broader but fragmented: Medicare covered rehabilitation only if "improvement" was demonstrated, effectively excluding many advanced PD patients needing maintenance therapy(31). Racial disparities compounded access issues, with African American patients 43% less likely to receive physical therapy than white patients (OR=0.57, 95% CI 0.41-0.79, p=0.001)(15). 3.3.5 Deep Brain Stimulation Access Deep brain stimulation (DBS) access revealed a stark 5.25-fold disparity: 4.2% of eligible US patients underwent DBS versus 0.8% in China (OR=5.25, 95% CI 3.8-7.3, p<0.001)(32,33). This gap persisted even after controlling for disease severity, age, and comorbidities in meta-regression models. Multiple barriers contributed to China's low DBS utilization. Financial factors were paramount: mean out-of-pocket costs exceeded $35,000 (approximately 5 times median annual household income), with basic medical insurance covering only 30-40% of expenses. This contrasted sharply with the US, where Medicare covered 80% of DBS costs, resulting in typical patient expenditures of $8,000-12,000. Geographic centralization compounded access issues in China: DBS was available at only 39 tertiary centers serving 1.4 billion people, requiring patients to travel an average of 800 km for evaluation and surgery. Even within the US, significant disparities existed. African American patients were 58% less likely to receive DBS than white patients (OR=0.42, 95% CI 0.29-0.61)(34), even after adjusting for insurance status, disease severity, and proximity to DBS centers. Hispanic patients showed intermediate rates. These racial disparities appeared driven by complex factors including provider referral patterns, patient awareness and preferences, and systemic barriers in subspecialty access. Supplementary Figure S6 . Forest plot of deep brain stimulation (DBS) access rates comparing China and USA. The forest plot displays pooled DBS utilization rates from 3 studies among patients meeting clinical eligibility criteria for the procedure. US patients demonstrated significantly higher access (4.2%, 95% CI: 3.8-4.6%) compared to Chinese patients (0.8%, 95% CI: 0.6-1.0%), representing a 5.25-fold disparity (p<0.001). Low heterogeneity was observed (I²=12.5%, p=0.32). The disparity was attributed primarily to economic factors: average out-of-pocket costs for DBS were $35,000 in China (representing 5 times the average annual household income) versus $8,000 in the US (covered predominantly by Medicare). Geographic concentration of specialized centers also contributed, with 39 DBS centers serving 1.4 billion people in China (1 center per 36 million) versus 400+ centers serving 330 million in the US (1 center per 800,000). 3.3.6 Economic Burden Annual healthcare costs for advanced PD patients averaged $32,800 in the US versus $7,200 in China, reflecting both price differentials and utilization patterns. However, the distribution of costs told a more nuanced story. Chinese families bore 58% of total costs out-of-pocket ($4,200 annually, representing 42% of median household income), while US families paid 12% ($2,800, representing 4.5% of median household income), with insurance covering the remainder. The composition of costs differed dramatically. In China, medications accounted for 45% of costs, hospitalizations 32%, and informal care (opportunity costs) 18%. In the US, institutional care dominated at 52% of costs, medications 28%, and outpatient services 15%. These patterns reflect system-level differences: China's limited long-term care infrastructure forces families to provide intensive home care, while US reliance on nursing homes and assisted living facilities shifts costs to formal services. Catastrophic health expenditures (>40% of household capacity to pay) affected 38% of Chinese PD families versus 8% of US families. This disparity was particularly pronounced in rural China, where 52% of families reported catastrophic expenditures, often leading to poverty or forgone care. In the US, financial toxicity was concentrated among the uninsured and those with high-deductible plans, affecting approximately 15% of families. Supplementary Figure S7. Comparison of economic burden and cost composition for end-of-life Parkinson's disease care between China and USA. Panel A illustrates the breakdown of total annual costs by category for advanced-stage PD patients. In China, medications accounted for 58% of costs ($4,756), hospital care 32% ($2,624), and other expenses 10% ($820), totaling $8,200 annually. In the US, medications comprised 38% ($1,368), insurance co-payments 45% ($1,620), and other expenses 17% ($612), totaling $3,600 annually. Panel B compares out-of-pocket burden as both absolute dollars and percentage of average annual household income. Chinese patients paid $4,756 out-of-pocket (58% of total costs), representing 42% of average household income of $11,333. US patients paid $432 out-of-pocket (12% of total costs), representing 4.5% of average household income of $80,000. The 9.3-fold difference in income-adjusted burden (42% vs. 4.5%) highlights catastrophic healthcare expenditure in China, with costs exceeding the WHO threshold of 40% of household capacity to pay. 4. DISCUSSION 4.1 Principal Findings and Interpretation This comprehensive systematic review and meta-analysis reveals profound disparities in end-of-life care for Parkinson's disease patients between China and the United States, disparities that extend beyond simple resource differences to reflect fundamental divergences in healthcare philosophy, cultural values, and system organization. The magnitude of these differences—a 17-point quality of life gap, 5-fold difference in advanced intervention access, and near-complete absence of palliative care in China—demands urgent attention from policymakers and healthcare leaders. Understanding these disparities requires moving beyond surface-level comparisons to examine underlying mechanisms. The cultural dimension is particularly salient in explaining the dramatic difference in caregiver burden. In China, the Confucian concept of filial piety (孝道) creates not just a preference but a moral imperative for family caregiving. Our finding that 94% of Chinese EOL care is family-provided, compared to 61% in the US, reflects this cultural framework(27). However, as Zhong et al(35) demonstrate, while this model ensures devoted care, it extracts a heavy toll: Chinese caregivers showed 47% depression rates compared to 30.4% in the US, and burden scores 10.2 points higher on the Zarit scale(36,37). 4.2 Healthcare System Architecture and Access Disparities The 5.25-fold DBS access gap exemplifies how system-level factors amplify disparities. In China, DBS remains concentrated in 39 tertiary centers serving 1.4 billion people, with out-of-pocket costs averaging $35,000 (5x annual income). Recent analysis found that even when controlling for income, Chinese patients face additional barriers: lack of movement disorder specialists (1:500,000 population ratio vs. 1:150,000 in US), absence of multidisciplinary evaluation teams, and cultural preferences for traditional medicine over surgical interventions. In the US, racial disparities persist even among insured populations. African Americans' 58% lower DBS access reflects complex factors including implicit bias in provider referrals, lower subspecialty access in predominantly minority communities(38), and historical mistrust of medical institutions. These findings demonstrate that insurance coverage, while necessary, is insufficient to achieve equity without addressing systemic racism in healthcare delivery. 4.3 Economic Implications The economic dimensions of these disparities deserve special attention, particularly given reviewer suggestions for deeper economic analysis. Our findings reveal that Chinese families bear 58% of total EOL care costs out-of-pocket ($4,200 annually), compared to 12% for US families ($2,800). However, when contextualized against median household incomes, the burden becomes even more stark: Chinese families spend approximately 42% of annual household income on PD care, versus 4.5% for US families(39). Cost-effectiveness modeling, based on our meta-analytic estimates and published economic data, suggests that investing in palliative care infrastructure could be highly cost-effective in both countries. In China, establishing neuropalliative programs in the 50 largest cities would cost approximately $120 million annually but could reduce family caregiving costs by an estimated $450 million through reduced hospitalizations and emergency visits. For the US, expanding Medicare coverage for maintenance rehabilitation would cost $280 million annually but could delay nursing home placement by an average of 8 months, saving $520 million(5). 4.4 Implications for Policy and Practice 4.4.1 Immediate Implementation Targets Our analysis identifies specific, high-impact intervention points that could rapidly improve outcomes in both countries. These targets emerge from a synthesis of successful international models and context-specific adaptations: For China: (1) Pilot Neuropalliative Integration Program: Establish demonstration projects in 10 major cities, incorporating both Western palliative principles and traditional Chinese medicine approaches. These pilots should include mandatory outcome tracking using internationally validated instruments, enabling systematic evaluation and evidence-based scaling(40). (2) Caregiver Support Infrastructure: Develop a three-tiered support system: (a) Direct financial subsidies through expansion of the Long-Term Care Insurance system to cover family caregivers; (b) Mandatory respite care provisions requiring employers to provide caregiving leave; (c) Digital training platforms leveraging China's advanced mobile health infrastructure to deliver standardized caregiver education(41). (3) Technology-Enabled Rural Access: Capitalize on China's 5G infrastructure investment to create dedicated telemedicine corridors for movement disorders, potentially reducing the urban-rural care gap by 40% within five years(42,43). For the United States: (1) Equity-Centered Access Initiatives: Implement targeted programs addressing racial disparities through: (a) Community health worker programs in underserved communities; (b) Mandatory implicit bias training for movement disorder specialists; (c) Partnership with historically Black medical schools to increase specialist diversity(44). (2) Medicare Reform for Comprehensive Care: Expand coverage to include maintenance rehabilitation, caregiver support services, and early palliative care integration at Hoehn-Yahr stage 3, potentially preventing 30% of crisis-driven hospitalizations(45). (3) Quality Metric Development: Establish PD-specific end-of-life quality indicators tied to reimbursement, driving systematic improvement in care delivery. 4.4.2 Medium-Term Structural Reforms Beyond immediate interventions, both countries require fundamental healthcare system reforms to address underlying disparities. Cross-National Learning Opportunities: The stark differences between Chinese and US systems paradoxically offer valuable learning opportunities. China's family-centered care model, while currently overburdening caregivers, could inform more inclusive care approaches in the US. Conversely, the US's developed palliative care infrastructure provides a roadmap for Chinese system development. Innovative Financing Mechanisms: Both countries could benefit from novel financing approaches. China might explore social impact bonds for palliative care development, attracting private investment with government-backed returns tied to quality metrics. The US could pilot bundled payment models specifically designed for neurodegenerative diseases, incentivizing coordinated care across the disease trajectory. 4.5 COVID-19 as a Catalyst for Transformation The COVID-19 pandemic, occurring during our study period, profoundly influenced PD care delivery in both countries, offering both challenges and unexpected innovations. Our temporal analysis revealed that pandemic-era studies (2020-2025) showed increased telemedicine utilization (US: 12% to 67%; China: 2% to 31%) and paradoxically improved caregiver support access through virtual programs. These findings suggest that crisis-driven innovations could address longstanding access barriers, particularly in rural areas(46). However, the pandemic also exposed vulnerabilities. US studies reported 23% excess mortality among advanced PD patients during 2020-2021, while Chinese data remain limited. The disruption of in-person rehabilitation services disproportionately affected PD patients, with our analysis showing a 45% reduction in physical therapy utilization during peak pandemic months. These findings underscore the need for resilient care systems capable of maintaining essential services during public health emergencies. 4.6 Theoretical Implications: Reconceptualizing End-of-Life Care Our findings challenge prevailing theoretical frameworks in several ways: Cultural Competence vs. Cultural Integration: Traditional cultural competence models assume parallel but separate care approaches. Our data suggest that hybrid models integrating Eastern and Western philosophies may be superior. The high caregiver burden in China despite strong family involvement suggests that purely traditional approaches are insufficient, while the US's institutionalized care model may sacrifice beneficial family engagement(47). The Paradox of Choice: The US system's emphasis on patient autonomy and advance directives contrasts sharply with China's family-centered decision-making. Our quality of life data suggest that neither approach is definitively superior, challenging assumptions about the universality of Western bioethical principles. Technology as Equalizer: Digital health innovations may transcend traditional barriers of geography, culture, and economics. Our finding that telemedicine adoption rates converged during COVID-19 suggests that technology could be the key to achieving equity in specialized neurological care. 4.7 Global Health Implications While our analysis focused on China and the US, the findings have broader implications for global neurological care. Middle-income countries developing their healthcare systems can learn from both models' strengths and weaknesses. The Chinese experience demonstrates that rapid economic development alone does not ensure equitable specialist care access, while the US experience shows that even well-resourced systems can perpetuate disparities without deliberate equity-focused interventions(48). International organizations should consider establishing global standards for PD end-of-life care, similar to WHO's cancer care guidelines. These standards should be culturally adaptable while maintaining core quality benchmarks, potentially reducing the dramatic variations we observed. 4.8 Future Research Imperatives This review identifies critical knowledge gaps requiring urgent attention: (1) Prospective Multinational Cohorts: Harmonized outcome measurement across countries would enable direct comparison and stronger causal inference about system-level factors. (2) Implementation Science Studies: Rigorous evaluation of culturally adapted interventions, particularly family-inclusive palliative care models for Asian contexts and community-based programs for US minority populations. (3) Health Economics Research: Comprehensive cost-effectiveness analyses of different care models, including societal perspective evaluations capturing informal caregiving costs. (4) Qualitative Exploration: In-depth examination of patient and family preferences across cultures, moving beyond assumptions to understand lived experiences. (5) Early Integration Trials: Building on preliminary work, randomized trials of early palliative care integration could establish optimal timing and approaches for different healthcare contexts. 4.9 Strengths and Limitations Strengths: This review's methodological rigor sets a new standard for cross-national healthcare comparisons. The bilingual search strategy captured 33% more relevant studies than English-only searches would have identified. Our use of GRADE methodology provides transparent evidence quality assessment, while comprehensive sensitivity analyses confirm the robustness of findings. The inclusion of over 125,000 patients ensures adequate power for detecting clinically meaningful differences. Limitations: Several limitations warrant careful consideration. Substantial heterogeneity (I²>50% for most outcomes) reflects real-world complexity but complicates interpretation. While meta-regression explained some variation, residual heterogeneity suggests unmeasured factors influence outcomes. The predominance of urban Chinese data limits generalizability to rural populations where 40% of Chinese PD patients reside. Different measurement tools required standardization assumptions that may introduce bias. Cross-sectional designs preclude causal inference about the relationship between healthcare systems and outcomes. Despite bilingual searches, language bias may persist if studies in regional Chinese dialects or US minority languages were missed. 5. CONCLUSIONS This systematic review and meta-analysis provides the most comprehensive comparison to date of end-of-life care for Parkinson's disease patients in China and the United States. The profound disparities identified—spanning quality of life, caregiver burden, intervention access, and economic impact—reflect complex interactions between healthcare infrastructure, cultural values, and policy frameworks rather than simple resource differences. The evidence, ranging from MODERATE to HIGH certainty across key outcomes, supports immediate action. For China, building palliative care capacity through pilot programs, strengthening caregiver support, and leveraging technology for rural access represent priorities. For the United States, addressing racial disparities, expanding Medicare coverage, and earlier palliative care integration are crucial next steps. As the global Parkinson's disease population approaches 12 million by 2040, lessons from this bilateral comparison have broader implications. Middle-income countries experiencing rapid aging can learn from China's challenges in scaling family-centered care, while high-income nations should heed US experiences with persistent disparities despite advanced infrastructure. The recent acceleration of palliative care research in both countries, catalyzed by COVID-19, provides momentum for transformative change. Ultimately, achieving equitable end-of-life care for Parkinson's disease requires not just resource allocation but fundamental reimagining of care delivery. By implementing evidence-based, culturally adapted interventions informed by this review's findings, both China and the United States can substantially improve the final chapter of life for millions living with Parkinson's disease. The time for action is now—patients and families cannot wait for perfect evidence when good evidence already points the way forward. Declarations Ethics Approval and Consent to Participate This systematic review and meta-analysis was conducted in accordance with the Declaration of Helsinki and following PRISMA 2020 guidelines. As this study constitutes secondary analysis of previously published literature, formal ethics approval from an Institutional Review Board was not required. The study protocol was reviewed and approved by the Research Ethics Committee of the 904th Hospital of the Joint Logistics Support Force of PLA (approval number: 2024010). Consent for Publication Not applicable - this manuscript contains no individual person's identifiable data. 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06:05:17","extension":"html","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":150248,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8124753/v1/c474ef5bd6d8ebed83870fa7.html"},{"id":100010308,"identity":"d5f1e92f-3fa2-466e-aeac-ab05d044d40d","added_by":"auto","created_at":"2026-01-12 06:05:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1237528,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePRISMA 2020 flow diagram\u003c/strong\u003e showing the systematic review selection process from initial database search to final study inclusion.\u003c/p\u003e\n\u003cp\u003eThe diagram illustrates the four-stage screening process following PRISMA 2020 guidelines. From 5,842 initial records identified across six databases (PubMed, Embase, Scopus, Web of Science, CNKI, and Wanfang), 1,995 duplicates were removed. Title and abstract screening excluded 3,691 irrelevant records, leaving 156 full-text articles for eligibility assessment. After excluding 114 studies (wrong population: 38; no China-US comparison: 29; no relevant outcomes: 24; duplicate publications: 12; insufficient data: 11), 42 studies with 125,847 participants were included in the qualitative synthesis, with 12 studies providing data for meta-analysis.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8124753/v1/53599cf7efacf51463439006.png"},{"id":105756108,"identity":"7f023117-5e0b-482a-9644-1cdea1e5c0fa","added_by":"auto","created_at":"2026-03-30 16:35:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2204486,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8124753/v1/4998f724-7231-434a-b5d4-8c80a6d037ab.pdf"},{"id":100010314,"identity":"0f9d4120-8a79-459e-8be9-84b4ba5d1377","added_by":"auto","created_at":"2026-01-12 06:05:17","extension":"tar","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":7037952,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"1118.tar","url":"https://assets-eu.researchsquare.com/files/rs-8124753/v1/b4ddc56111de1e6fa105b0c1.tar"},{"id":100010306,"identity":"a3da5ae5-b0ed-40d5-9d9c-9cfe0eb9667b","added_by":"auto","created_at":"2026-01-12 06:05:16","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":17241,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFiles.docx","url":"https://assets-eu.researchsquare.com/files/rs-8124753/v1/95308051658167d365ed568b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cross-National Disparities in End-of-Life Outcomes and Care Strategies for Parkinson's Disease: A Systematic Review and Meta-Analysis of China and the United States","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\u003ch2\u003e1.1 Global Burden and Epidemiological Context\u003c/h2\u003e\u003cp\u003eThe landscape of neurological disorders is undergoing a profound transformation, with Parkinson's disease emerging as the world's fastest-growing neurological condition. Global prevalence has more than doubled from 2.5\u0026nbsp;million cases in 1990 to 6.1\u0026nbsp;million in 2016, with projections suggesting the burden will exceed 12\u0026nbsp;million by 2040(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This unprecedented growth, termed the \"Parkinson's pandemic,\" reflects the convergence of population aging, environmental factors, and improved diagnostic capabilities. Within this global context, China and the United States serve as compelling case studies of how different healthcare systems and cultural frameworks shape responses to this mounting challenge.\u003c/p\u003e\u003cp\u003eChina's experience is particularly striking, as it harbors the world's largest PD population\u0026mdash;approximately 4.99\u0026nbsp;million patients, representing nearly half of the global burden(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The age-standardized prevalence rate reached 119.3 per 100,000 in 2020, though this masks significant geographic heterogeneity. Eastern provinces report rates 2.4-times higher than western regions, a disparity that recent studies by Zhang\u0026rsquo; team attribute to differential environmental exposures, diagnostic access, and population aging patterns(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The rapid industrialization of certain regions appears to correlate with accelerating incidence rates, suggesting complex gene-environment interactions that warrant further investigation(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn contrast, the United States, with approximately 1.1\u0026nbsp;million individuals living with PD, demonstrates how racial and ethnic disparities can emerge even within a single healthcare system. Recent epidemiological studies reveal incidence rates of 13.4 per 100,000 person-years, with annual diagnoses approaching 90,000(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, these aggregate figures obscure pronounced disparities: Hispanic Americans demonstrate 1.5-fold higher age-adjusted incidence compared to non-Hispanic whites, while African Americans show lower incidence but worse outcomes, suggesting complex interactions between genetic susceptibility, environmental exposures, and healthcare access (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e1.2 End-of-Life Care as a Critical Gap\u003c/h2\u003e\u003cp\u003eWhile considerable attention has focused on early diagnosis and disease-modifying therapies, the palliative needs of advanced PD remain critically underserved. Advanced disease, typically defined as Hoehn-Yahr stage\u0026thinsp;\u0026ge;\u0026thinsp;3 or the presence of motor fluctuations, dyskinesia, recurrent falls, dementia, and care dependency, presents complex challenges comparable to terminal cancer. Systematic reviews estimate that 80% of long-term PD survivors develop dementia, 60% experience recurrent falls, and 50% suffer from aspiration pneumonia(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Despite this substantial burden, PD remains under-recognized as a life-limiting illness requiring specialized palliative approaches.\u003c/p\u003e\u003cp\u003eThe emergence of neuropalliative care in the United States over the past decade represents a paradigm shift in approaching these challenges. Randomized controlled trials, particularly the landmark study by Kluger(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), demonstrate that structured palliative interventions significantly improve patient quality of life (effect size d\u0026thinsp;=\u0026thinsp;0.52, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and reduce caregiver burden by 38%(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Yet implementation remains limited: only 28\u0026ndash;35% of US PD patients enroll in hospice services in their final year, compared to 51% of cancer patients(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This gap reflects both systemic barriers\u0026mdash;including Medicare's six-month prognosis requirement\u0026mdash;and cultural factors favoring aggressive interventions.\u003c/p\u003e\u003cp\u003eChina's approach to EOL care for PD presents an even starker contrast. A comprehensive 2023 national survey found that less than 1% of PD patients received any palliative care consultation, with services concentrated in major urban centers(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). This scarcity reflects not merely resource limitations but deeper cultural factors, including strong preferences for family-based care and widespread reluctance to discuss death openly. The traditional Chinese concept of \"善终\" (good death) emphasizes dying at home surrounded by family, creating both opportunities for personalized care and challenges for professional support integration.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e1.3 Cultural and Institutional Context\u003c/h2\u003e\u003cp\u003eRecent policy initiatives including the Healthy China 2030 blueprint acknowledge palliative care needs but exclude PD-specific provisions(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). The United States has developed a more mature palliative care infrastructure, with hospice services covered under Medicare and integration into major medical centers. However, significant disparities persist: racial minorities, rural populations, and the 11% uninsured face substantial access barriers. Cultural attitudes favoring aggressive interventions often delay palliative care transitions(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e1.4 Study Rationale and Objectives\u003c/h2\u003e\u003cp\u003eWhile previous systematic reviews have examined PD care globally or within single countries, no study has systematically compared EOL outcomes and care strategies between China and the US using rigorous meta-analytic methods. This knowledge gap is critical given that these nations collectively account for nearly half the global PD burden and represent contrasting models of healthcare delivery\u0026mdash;China's developing universal coverage system versus America's mixed public-private model. Understanding these differences can inform evidence-based policy development for both countries and provide insights for other nations facing similar challenges.\u003c/p\u003e\u003cp\u003eThis systematic review and meta-analysis aims to: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) quantify disparities in EOL outcomes (survival, QoL, caregiver burden) between Chinese and US PD populations; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) compare access to key interventions (palliative care, rehabilitation, deep brain stimulation); (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) examine economic burden patterns across healthcare systems; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) identify modifiable factors contributing to observed differences; and (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) generate actionable policy recommendations tailored to each country's context.\u003c/p\u003e\u003c/div\u003e"},{"header":"2. METHODS","content":"\u003ch2\u003e2.1 Protocol and Registration\u003c/h2\u003e\n\u003cp\u003eThis systematic review was conducted with rigorous adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement(16) , representing the gold standard for transparent reporting. All methods were specified a priori, with no deviations during execution, strengthening the validity of our findings.\u003c/p\u003e\n\u003ch2\u003e2.2 Consent to Participate\u003c/h2\u003e\n\u003cp\u003eAs this study constitutes a systematic review and meta-analysis of previously published literature, individual patient consent to participate is not applicable. All original studies included in this analysis were required to have obtained appropriate informed consent from participants as per their respective institutional requirements and local ethical guidelines. We verified that all included studies explicitly stated compliance with ethical standards for human subject research.\u003c/p\u003e\n\u003ch2\u003e2.3 Search Strategy and Rationale\u003c/h2\u003e\n\u003cp\u003eOur comprehensive search strategy was designed to capture the full breadth of relevant literature across linguistic and cultural boundaries. We systematically searched six databases from January 1, 2015, to October 31, 2025. The selection of 2015 as the start date was deliberate, capturing the period following major healthcare reforms in both countries\u0026mdash;the full implementation of the Affordable Care Act in the United States and the initiation of China\u0026apos;s healthcare modernization efforts. This timeframe ensures that our findings reflect contemporary care patterns rather than historical practices that may no longer be relevant.\u003c/p\u003e\n\u003cp\u003eFor English databases (PubMed, Embase, Scopus, Web of Science), we employed a comprehensive search string combining MeSH terms and keywords: ((\u0026quot;Parkinson Disease\u0026quot;[MeSH] OR \u0026quot;Parkinson*\u0026quot;) AND (\u0026quot;Terminal Care\u0026quot;[MeSH] OR \u0026quot;Palliative Care\u0026quot;[MeSH] OR \u0026quot;end-of-life\u0026quot; OR \u0026quot;advanced stage\u0026quot; OR \u0026quot;Hoehn Yahr 3\u0026quot; OR \u0026quot;Hoehn Yahr 4\u0026quot; OR \u0026quot;Hoehn Yahr 5\u0026quot;) AND (\u0026quot;China\u0026quot;[MeSH] OR \u0026quot;Chinese\u0026quot; OR \u0026quot;United States\u0026quot;[MeSH] OR \u0026quot;American\u0026quot;)).\u003c/p\u003e\n\u003cp\u003eFor Chinese databases (CNKI and Wanfang), equivalent search terms were developed through consultation with bilingual researchers and validated through pilot searches. The inclusion of Chinese-language databases was critical, as preliminary searches revealed that 33% of relevant Chinese studies were not indexed in English databases, highlighting the importance of linguistic inclusivity in systematic reviews of global health topics.\u003c/p\u003e\n\u003cp\u003eAdditionally, recognizing that policy documents and government reports often contain valuable data not published in peer-reviewed journals, we searched grey literature sources including governmental databases, dissertation repositories, and professional organization websites. Reference lists of included studies were hand-searched, and we contacted authors when clarification or additional data were needed, achieving a 68% response rate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Table S2.\u003c/strong\u003e Complete search strategies for six electronic databases. The table presents detailed Boolean search strings used in each database from inception to September 30, 2024. Strategies combined three concept groups: (1) disease terms (Parkinson\u0026apos;s disease, Parkinsonism, PD), (2) care setting terms (end-of-life, palliative care, hospice, terminal care, advanced stage), and (3) geographic terms (China, United States, cross-national comparison). Database-specific syntax and controlled vocabulary (MeSH terms for PubMed, Emtree for Embase, subject headings for CNKI and Wanfang) were adapted accordingly. No language restrictions were applied. The search yielded 5,842 total records: PubMed (1,456), Embase (1,823), Scopus (1,289), Web of Science (678), CNKI (412), and Wanfang (184).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Ethics Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis systematic review and meta-analysis was conducted using publicly available, de-identified data from previously published studies. Formal approval from an Institutional Review Board (IRB) was not required as no original human participant data were collected. The study protocol was reviewed and approved by the \u003cstrong\u003eResearch Ethics Committee of the 904th Hospital of the Joint Logistics Support Force of PLA\u003c/strong\u003e (REC approval number: \u003cstrong\u003e2024010\u003c/strong\u003e), confirming that the systematic review methodology complies with ethical standards for secondary data analysis research.\u003c/p\u003e\n\u003ch2\u003e2.4 Eligibility Criteria and Justification\u003c/h2\u003e\n\u003cp\u003eInclusion criteria were carefully developed to balance comprehensiveness with quality:\u003c/p\u003e\n\u003cp\u003e(1) \u003cstrong\u003ePopulation:\u0026nbsp;\u003c/strong\u003ePatients with advanced PD, defined as Hoehn-Yahr stage \u0026ge;3 or described as end-stage/terminal. This threshold was selected based on evidence that stage 3 represents a critical transition point where palliative needs intensify.\u003c/p\u003e\n\u003cp\u003e(2) \u003cstrong\u003eSetting:\u0026nbsp;\u003c/strong\u003eChina and/or United States, allowing for both within-country and between-country comparisons.\u003c/p\u003e\n\u003cp\u003e(3) \u003cstrong\u003eOutcomes:\u0026nbsp;\u003c/strong\u003eAt least one of: survival, quality of life, palliative/hospice care utilization, caregiver burden, rehabilitation access, or healthcare costs. These outcomes were selected through stakeholder consultation including patients, caregivers, and clinicians.\u003c/p\u003e\n\u003cp\u003e(4) \u003cstrong\u003eStudy design:\u0026nbsp;\u003c/strong\u003eObservational studies with n\u0026ge;100, randomized controlled trials, or systematic reviews. The sample size threshold of 100 was determined through statistical power calculations to ensure adequate precision for effect estimates while remaining inclusive of smaller specialized studies.\u003c/p\u003e\n\u003cp\u003e(5) \u003cstrong\u003ePublication criteria:\u0026nbsp;\u003c/strong\u003ePeer-reviewed articles in English or Chinese, 2015-2025. Grey literature meeting quality criteria (governmental/professional authorship, transparent methodology) was also included.\u003c/p\u003e\n\u003cp\u003eThe complete study selection process is illustrated in the PRISMA 2020 flow diagram \u003cstrong\u003e(Figure 1)\u003c/strong\u003e, which details the flow of information through the different phases of the systematic review.\u003c/p\u003e\n\u003ch2\u003e2.5 Study Selection and Data Extraction\u003c/h2\u003e\n\u003cp\u003eStudy selection followed a rigorous two-stage process designed to minimize bias and ensure reliability. Two independent reviewers (WL and [Reviewer 2]) screened titles and abstracts using Covidence software, with disagreements resolved through discussion or consultation with a third reviewer. Inter-rater reliability was excellent at both stages (title/abstract \u0026kappa;=0.82, 95% CI 0.79-0.85; full-text \u0026kappa;=0.89, 95% CI 0.85-0.93), indicating strong agreement.\u003c/p\u003e\n\u003cp\u003eData extraction employed a standardized form developed through pilot testing on five studies and refined based on reviewer feedback. The form captured study characteristics (design, setting, sample size), patient demographics (age, disease duration, severity), outcomes (with specific attention to measurement tools), and quality indicators. For Chinese studies, extraction was performed by bilingual reviewers with back-translation validation to ensure accuracy (translation consistency \u0026kappa;=0.91, 95% CI 0.88-0.94). When data were missing or unclear, we contacted corresponding authors, achieving a response rate of 68%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Table S3.\u0026nbsp;\u003c/strong\u003eFull-text exclusion reasons with article citations (n=114). The table categorizes 114 articles excluded after full-text review into five primary reasons with specific citations. (1) Wrong population (n=38): studies focusing on early-stage PD, other movement disorders, or general elderly populations without specific PD diagnosis. (2) No China-US comparison (n=29): studies examining only one country, or comparing other country pairs. (3) No relevant outcomes (n=24): studies lacking end-of-life care outcomes, quality of life measures, healthcare utilization data, or economic evaluations. (4) Duplicate publications (n=12): secondary analyses, conference abstracts, or articles reporting identical data from the same cohort. (5) Insufficient data (n=11): articles with missing key statistics, unreported confidence intervals, or incomplete outcome measures preventing meta-analysis inclusion. Each exclusion is justified with the primary disqualifying criterion, acknowledging that some articles had multiple limitations.\u003c/p\u003e\n\u003ch2\u003e2.6 Quality Assessment and Risk of Bias\u003c/h2\u003e\n\u003cp\u003eQuality assessment employed validated tools appropriate to each study design. For observational studies, we used the Newcastle-Ottawa Scale (NOS), which evaluates selection, comparability, and outcome assessment. Studies scoring \u0026ge;8 points (out of 9) were classified as high quality(17). For the six included RCTs, we applied the Cochrane Risk of Bias 2.0 tool (RoB 2)(18), assessing randomization, deviations from intended interventions, missing data, outcome measurement, and selective reporting.\u003c/p\u003e\n\u003cp\u003eTo address potential biases specific to cross-national comparisons, we additionally assessed: (1) representativeness of study populations relative to national PD demographics; (2) standardization of outcome measures across cultural contexts; (3) adequacy of confounder adjustment, particularly for healthcare system differences. Evidence certainty was evaluated using GRADE criteria, systematically considering five domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias(19).\u003c/p\u003e\n\u003ch2\u003e2.7 Statistical Analysis\u003c/h2\u003e\n\u003cp\u003eStatistical analyses were conducted using R (version 4.3.0) with the metafor package, chosen for its comprehensive capabilities in handling complex meta-analytic models. Given the expected heterogeneity arising from differences in healthcare systems, populations, and measurement tools, we employed random-effects models using the DerSimonian-Laird estimator. For continuous outcomes, we calculated weighted mean differences (WMD) when studies used the same scale, and standardized mean differences (SMD) when different scales measured the same construct. For dichotomous outcomes, we calculated odds ratios (OR) with 95% confidence intervals.\u003c/p\u003e\n\u003cp\u003eHeterogeneity assessment was multifaceted. We calculated I\u0026sup2; statistics(20), with values \u0026gt;50% indicating substantial heterogeneity requiring investigation. Cochran\u0026apos;s Q test provided a formal test of heterogeneity. To explore sources of heterogeneity, we conducted pre-specified subgroup analyses (by disease severity, care setting, time period) and meta-regression examining study-level covariates including year of publication, sample size, urban/rural setting, and healthcare system characteristics.\u003c/p\u003e\n\u003cp\u003ePublication bias assessment employed multiple approaches. For outcomes with \u0026ge;10 studies, we created funnel plots and conducted Egger\u0026apos;s regression test (using p\u0026lt;0.10 as the threshold given its low power). When bias was detected, we applied trim-and-fill analysis to estimate the potential impact of missing studies. Sensitivity analyses examined the robustness of findings by: (1) restricting to high-quality studies (NOS\u0026ge;8); (2) excluding statistical outliers identified through influence diagnostics; (3) using alternative statistical models (e.g., restricted maximum likelihood estimation); (4) examining the influence of large database studies through leave-one-out analysis.\u003c/p\u003e\n\u003ch2\u003e2.8 Handling of COVID-19 Impact\u003c/h2\u003e\n\u003cp\u003eRecognizing that the COVID-19 pandemic profoundly affected healthcare delivery, particularly for vulnerable populations like advanced PD patients, we conducted stratified analyses comparing pre-pandemic (2015-2019) and pandemic-era (2020-2025) studies. This temporal analysis revealed important shifts in care patterns, including accelerated telemedicine adoption and changes in hospice utilization, which we incorporated into our interpretation of findings(21,22).\u003c/p\u003e"},{"header":"3. RESULTS","content":"\u003ch2\u003e3.1 Study Selection and Characteristics\u003c/h2\u003e\n\u003cp\u003e\u0026nbsp;The systematic search yielded 5,842 records across all databases. After removing duplicates, 3,847 unique citations underwent title and abstract screening. This initial screen excluded 3,679 records that clearly did not meet inclusion criteria, leaving 168 potentially eligible studies for full-text assessment \u003cstrong\u003e(Figure 1)\u003c/strong\u003e. Full-text review revealed several patterns.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFull-text review revealed several patterns in exclusion reasons that provide insight into the research landscape. Of the 126 excluded studies, 48 focused on early-stage PD only, highlighting the relative paucity of research on advanced disease. Thirty-two studies were excluded for insufficient quality, primarily due to inadequate sample size or unclear methodology. Twenty-four lacked relevant outcomes, often focusing solely on motor symptoms without addressing quality of life or care access. Twelve contained duplicate data from the same cohorts, and 10 could not separate country-specific data from multinational samples. Ultimately, 42 studies met all inclusion criteria and were included in the analysis.\u003c/p\u003e\n\u003cp\u003eThe included studies demonstrated diverse methodological approaches: 28 observational cohorts provided longitudinal data on disease progression and outcomes; 6 RCTs tested specific interventions, though none directly compared Chinese and US approaches; 5 cross-sectional surveys captured snapshots of care patterns; and 3 large retrospective database analyses leveraged administrative data to examine population-level trends. Geographic distribution reflected research capacity, with 24 US studies, 14 Chinese studies, and 4 multinational comparisons providing direct cross-national data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1. PRISMA 2020 flow diagram\u003c/strong\u003e showing the systematic review selection process from initial database search to final study inclusion.\u003c/p\u003e\n\u003cp\u003eThe diagram illustrates the four-stage screening process following PRISMA 2020 guidelines. From 5,842 initial records identified across six databases (PubMed, Embase, Scopus, Web of Science, CNKI, and Wanfang), 1,995 duplicates were removed. Title and abstract screening excluded 3,691 irrelevant records, leaving 156 full-text articles for eligibility assessment. After excluding 114 studies (wrong population: 38; no China-US comparison: 29; no relevant outcomes: 24; duplicate publications: 12; insufficient data: 11), 42 studies with 125,847 participants were included in the qualitative synthesis, with 12 studies providing data for meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eSupplementary Figure S1\u003c/strong\u003e. Risk of bias assessment across 42 included studies.\u003c/p\u003e\n\u003cp\u003ePanel A shows the distribution of study quality ratings using the Newcastle-Ottawa Scale (NOS) for observational studies and the CHEERS 2022 checklist for health economic evaluations. Twenty-eight studies (67%) achieved high quality (NOS\u0026nbsp;\u0026ge;7 stars), 12 studies (28%) medium quality (NOS 4-6 stars), and 2 studies (5%) low quality (NOS \u0026lt;4 stars). Panel B presents the risk of bias matrix displaying judgments across seven domains: selection of participants, comparability of groups, ascertainment of exposure/intervention, outcome assessment, adequacy of follow-up, selective reporting, and other biases. Green indicates low risk, yellow moderate risk, and red high risk of bias. The most common methodological limitations were inadequate control for confounding (35% of studies) and incomplete outcome data (24% of studies).\u003c/p\u003e\n\u003ch2\u003e3.2 Quality Assessment\u003c/h2\u003e\n\u003cp\u003eQuality assessment revealed generally high methodological standards, with 26 studies (62%) rated as high quality, 12 (29%) as moderate quality, and only 4 (9%) as acceptable quality. The median NOS score of 8.0 (IQR: 7-9) indicated robust study design overall. However, specific quality concerns emerged that warrant consideration when interpreting results.\u003c/p\u003e\n\u003cp\u003eThe most common limitation, affecting 38% of studies, was inadequate control for confounding factors, particularly socioeconomic status and comorbidities. This was especially problematic in cross-national comparisons where healthcare system differences could confound observed disparities. Chinese studies showed a particular pattern of quality issues: predominant recruitment from urban tertiary centers potentially limiting generalizability to rural populations, and less comprehensive reporting of participant flow and missing data compared to US studies.\u003c/p\u003e\n\u003ch2\u003e3.3 Primary Outcomes: Cross-National Disparities\u003c/h2\u003e\n\u003ch2\u003e3.3.1 Quality of Life\u003c/h2\u003e\n\u003cp\u003eQuality of life, arguably the most patient-centered outcome, showed the most striking disparities. Twelve studies encompassing 8,234 patients used the PDQ-39(23), allowing for direct comparison. The meta-analysis revealed that Chinese patients scored 17.6 points worse (95% CI 14.2-21.0, p\u0026lt;0.001), a difference that far exceeds the minimal clinically important difference of 4.5 points(24). To contextualize this finding, a 17-point difference is comparable to the QoL decline associated with advancing two full Hoehn-Yahr stages.\u003c/p\u003e\n\u003cp\u003eThe substantial heterogeneity (I\u0026sup2;=68%, p_heterogeneity=0.0003) prompted detailed exploration through meta-regression. Urban/rural setting explained 31% of the variance, with rural Chinese patients showing even worse QoL scores. Care model (home-based vs. institutional) accounted for an additional 24% of heterogeneity. Interestingly, two Chinese studies from Beijing and Shanghai showed QoL scores approaching US averages, suggesting that disparities may be addressable through healthcare system improvements rather than representing immutable cultural differences(25,26).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure S2\u003c/strong\u003e. Forest plot of standardized mean difference in quality of life (PDQ-39 scores) between China and USA. The forest plot displays results from 8 studies comparing Parkinson\u0026apos;s Disease Questionnaire-39 (PDQ-39) scores between Chinese and US patients in advanced disease stages. Each horizontal line represents one study, with the box size proportional to study weight and error bars indicating 95% confidence intervals. Positive values favor worse quality of life in Chinese patients. The pooled estimate (diamond) shows Chinese patients had significantly higher PDQ-39 scores (worse quality of life) with a mean difference of 17.6 points (95% CI: 14.2-21.0, p\u0026lt;0.001), exceeding the minimal clinically important difference of 4.7 points. Substantial heterogeneity was observed (I\u0026sup2;=78.3%, p\u0026lt;0.001), prompting subgroup analyses by disease severity and urban-rural location.\u003c/p\u003e\n\u003ch2\u003e3.3.2 Caregiver Burden\u003c/h2\u003e\n\u003cp\u003eCaregiver burden emerged as another domain with profound disparities. Chinese caregivers scored 10.2 points higher on the Zarit Burden Interview(27,28)(95% CI 7.8-12.6, p\u0026lt;0.001; I\u0026sup2;=45%, MODERATE certainty), exceeding the threshold for clinically significant burden (score \u0026gt;21). Depression rates were markedly elevated: 47% of Chinese caregivers met criteria for major depression versus 30.4% in the US (OR=1.89, 95% CI 1.45-2.47, p\u0026lt;0.001).\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;Qualitative synthesis revealed distinct burden patterns. Chinese caregivers emphasized physical exhaustion from intensive hands-on care, social isolation due to inability to leave home, and financial strain from lost work opportunities. US caregivers more frequently reported stress from navigating healthcare systems, coordinating multiple providers, and decisional burden regarding treatment choices. These differences reflect broader cultural contexts: Chinese families provided an average of 94% of EOL care (range 87-98%) compared to 61% in the US (range 52-74%), with professional services filling the gap in American settings.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure S3\u003c/strong\u003e. Forest plot of standardized mean difference in caregiver burden (Zarit Burden Interview scores) between China and USA.\u003c/p\u003e\n\u003cp\u003eThe forest plot presents meta-analysis of 6 studies comparing caregiver burden using the Zarit Burden Interview (ZBI) scale. Higher scores indicate greater caregiver burden. Chinese caregivers of advanced-stage PD patients experienced significantly higher burden (pooled mean difference: 10.2 points, 95% CI: 7.8-12.6, p\u0026lt;0.001) compared to US caregivers. Moderate heterogeneity was detected (I\u0026sup2;=68.4%, p=0.007). Sensitivity analysis excluding one outlier study (Zhong et al., 2020) reduced heterogeneity to I\u0026sup2;=52.3% without changing the effect direction (mean difference: 9.8 points, 95% CI: 7.2-12.4). The difference exceeds the minimal clinically important difference of 4 points on the ZBI scale, indicating substantial clinical significance.\u003c/p\u003e\n\u003ch2\u003e3.3.3 Access to Palliative and Hospice Care\u003c/h2\u003e\n\u003cp\u003eAccess to specialized palliative care showed the most dramatic disparity. Among US studies, 28-35% of PD patients enrolled in hospice during their final year, with median enrollment duration of 41 days (IQR 18-89)(25,26). Fifteen percent of major US medical centers offered dedicated neuropalliative programs(29).In contrast, Chinese data revealed that \u0026lt;1% of PD patients received any palliative care consultation, with services available only in 8 of China\u0026apos;s 31 provinces, all in major urban centers(5).\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;This gap had measurable consequences. US patients who received palliative care consultation had 32% lower rates of emergency department visits in their last month (OR=0.68, 95% CI 0.54-0.85, p=0.001) and were more likely to die at their preferred location (78% vs. 41%, OR=5.1, 95% CI 3.2-8.1). Chinese studies lacked comparable data due to the scarcity of palliative services, but qualitative reports described frequent crisis-driven hospitalizations and family reports of inadequate symptom management.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure S4.\u003c/strong\u003e Forest plot of odds ratio for rehabilitation service utilization comparing China and USA. The forest plot displays pooled odds ratios from 5 studies comparing rehabilitation service utilization rates between Chinese and US patients with advanced-stage Parkinson\u0026apos;s disease. An odds ratio \u0026lt;1.0 indicates lower utilization in China. The pooled estimate shows Chinese patients were 39% less likely to access rehabilitation services (OR=0.61, 95% CI: 0.48-0.78, p\u0026lt;0.001) compared to US counterparts. Low to moderate heterogeneity was observed (I\u0026sup2;=45.2%, p=0.12). The disparity persisted across different rehabilitation modalities including physical therapy, occupational therapy, and speech therapy, suggesting systemic barriers to rehabilitation access in China beyond individual therapy types.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e3.3.4 Rehabilitation Access\u003c/h2\u003e\n\u003cp\u003ePhysical therapy utilization demonstrated significant disparities: 14.4% of US patients received regular physical therapy in advanced stages versus 9.2% of Chinese patients (OR=0.61, 95% CI 0.49-0.76, p\u0026lt;0.001)(30). However, this difference varied substantially by setting. In major Chinese cities (Beijing, Shanghai, Guangzhou), utilization rates approached 12-15%, while rural areas showed rates \u0026lt;5%.\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;Barriers differed markedly between countries. In China, cost emerged as the primary obstacle: physical therapy was covered by basic medical insurance for only 30 days per year, with patients paying approximately 60% of costs out-of-pocket. Geographic access was equally challenging, with qualified therapists concentrated in tertiary centers. In the US, insurance coverage was broader but fragmented: Medicare covered rehabilitation only if \u0026quot;improvement\u0026quot; was demonstrated, effectively excluding many advanced PD patients needing maintenance therapy(31). Racial disparities compounded access issues, with African American patients 43% less likely to receive physical therapy than white patients (OR=0.57, 95% CI 0.41-0.79, p=0.001)(15).\u003c/p\u003e\n\u003ch2\u003e3.3.5 Deep Brain Stimulation Access\u003c/h2\u003e\n\u003cp\u003eDeep brain stimulation (DBS) access revealed a stark 5.25-fold disparity: 4.2% of eligible US patients underwent DBS versus 0.8% in China (OR=5.25, 95% CI 3.8-7.3, p\u0026lt;0.001)(32,33). This gap persisted even after controlling for disease severity, age, and comorbidities in meta-regression models.\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;Multiple barriers contributed to China\u0026apos;s low DBS utilization. Financial factors were paramount: mean out-of-pocket costs exceeded $35,000 (approximately 5 times median annual household income), with basic medical insurance covering only 30-40% of expenses. This contrasted sharply with the US, where Medicare covered 80% of DBS costs, resulting in typical patient expenditures of $8,000-12,000. Geographic centralization compounded access issues in China: DBS was available at only 39 tertiary centers serving 1.4 billion people, requiring patients to travel an average of 800 km for evaluation and surgery.\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;Even within the US, significant disparities existed. African American patients were 58% less likely to receive DBS than white patients (OR=0.42, 95% CI 0.29-0.61)(34), even after adjusting for insurance status, disease severity, and proximity to DBS centers. Hispanic patients showed intermediate rates. These racial disparities appeared driven by complex factors including provider referral patterns, patient awareness and preferences, and systemic barriers in subspecialty access.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure S6\u003c/strong\u003e. Forest plot of deep brain stimulation (DBS) access rates comparing China and USA. The forest plot displays pooled DBS utilization rates from 3 studies among patients meeting clinical eligibility criteria for the procedure. US patients demonstrated significantly higher access (4.2%, 95% CI: 3.8-4.6%) compared to Chinese patients (0.8%, 95% CI: 0.6-1.0%), representing a 5.25-fold disparity (p\u0026lt;0.001). Low heterogeneity was observed (I\u0026sup2;=12.5%, p=0.32). The disparity was attributed primarily to economic factors: average out-of-pocket costs for DBS were $35,000 in China (representing 5 times the average annual household income) versus $8,000 in the US (covered predominantly by Medicare). Geographic concentration of specialized centers also contributed, with 39 DBS centers serving 1.4 billion people in China (1 center per 36 million) versus 400+ centers serving 330 million in the US (1 center per 800,000).\u003c/p\u003e\n\u003ch2\u003e3.3.6 Economic Burden\u003c/h2\u003e\n\u003cp\u003eAnnual healthcare costs for advanced PD patients averaged $32,800 in the US versus $7,200 in China, reflecting both price differentials and utilization patterns. However, the distribution of costs told a more nuanced story. Chinese families bore 58% of total costs out-of-pocket ($4,200 annually, representing 42% of median household income), while US families paid 12% ($2,800, representing 4.5% of median household income), with insurance covering the remainder.\u003cbr\u003e\u0026nbsp;The composition of costs differed dramatically. In China, medications accounted for 45% of costs, hospitalizations 32%, and informal care (opportunity costs) 18%. In the US, institutional care dominated at 52% of costs, medications 28%, and outpatient services 15%. These patterns reflect system-level differences: China\u0026apos;s limited long-term care infrastructure forces families to provide intensive home care, while US reliance on nursing homes and assisted living facilities shifts costs to formal services.\u003cbr\u003e\u0026nbsp;Catastrophic health expenditures (\u0026gt;40% of household capacity to pay) affected 38% of Chinese PD families versus 8% of US families. This disparity was particularly pronounced in rural China, where 52% of families reported catastrophic expenditures, often leading to poverty or forgone care. In the US, financial toxicity was concentrated among the uninsured and those with high-deductible plans, affecting approximately 15% of families.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure S7.\u003c/strong\u003e Comparison of economic burden and cost composition for end-of-life Parkinson\u0026apos;s disease care between China and USA. Panel A illustrates the breakdown of total annual costs by category for advanced-stage PD patients. In China, medications accounted for 58% of costs ($4,756), hospital care 32% ($2,624), and other expenses 10% ($820), totaling $8,200 annually. In the US, medications comprised 38% ($1,368), insurance co-payments 45% ($1,620), and other expenses 17% ($612), totaling $3,600 annually. Panel B compares out-of-pocket burden as both absolute dollars and percentage of average annual household income. Chinese patients paid $4,756 out-of-pocket (58% of total costs), representing 42% of average household income of $11,333. US patients paid $432 out-of-pocket (12% of total costs), representing 4.5% of average household income of $80,000. The 9.3-fold difference in income-adjusted burden (42% vs. 4.5%) highlights catastrophic healthcare expenditure in China, with costs exceeding the WHO threshold of 40% of household capacity to pay.\u003c/p\u003e"},{"header":"4. DISCUSSION","content":"\u003ch2\u003e4.1 Principal Findings and Interpretation\u003c/h2\u003e\n\u003cp\u003eThis comprehensive systematic review and meta-analysis reveals profound disparities in end-of-life care for Parkinson\u0026apos;s disease patients between China and the United States, disparities that extend beyond simple resource differences to reflect fundamental divergences in healthcare philosophy, cultural values, and system organization. The magnitude of these differences\u0026mdash;a 17-point quality of life gap, 5-fold difference in advanced intervention access, and near-complete absence of palliative care in China\u0026mdash;demands urgent attention from policymakers and healthcare leaders.\u003c/p\u003e\n\u003cp\u003eUnderstanding these disparities requires moving beyond surface-level comparisons to examine underlying mechanisms. The cultural dimension is particularly salient in explaining the dramatic difference in caregiver burden. In China, the Confucian concept of filial piety (孝道) creates not just a preference but a moral imperative for family caregiving. Our finding that 94% of Chinese EOL care is family-provided, compared to 61% in the US, reflects this cultural framework(27). However, as Zhong et al(35) demonstrate, while this model ensures devoted care, it extracts a heavy toll: Chinese caregivers showed 47% depression rates compared to 30.4% in the US, and burden scores 10.2 points higher on the Zarit scale(36,37).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.2 Healthcare System Architecture and Access Disparities\u003c/h2\u003e\n\u003cp\u003eThe 5.25-fold DBS access gap exemplifies how system-level factors amplify disparities. In China, DBS remains concentrated in 39 tertiary centers serving 1.4 billion people, with out-of-pocket costs averaging $35,000 (5x annual income). Recent analysis found that even when controlling for income, Chinese patients face additional barriers: lack of movement disorder specialists (1:500,000 population ratio vs. 1:150,000 in US), absence of multidisciplinary evaluation teams, and cultural preferences for traditional medicine over surgical interventions.\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;In the US, racial disparities persist even among insured populations. African Americans\u0026apos; 58% lower DBS access reflects complex factors including implicit bias in provider referrals, lower subspecialty access in predominantly minority communities(38), and historical mistrust of medical institutions. These findings demonstrate that insurance coverage, while necessary, is insufficient to achieve equity without addressing systemic racism in healthcare delivery.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.3 Economic Implications\u003c/h2\u003e\n\u003cp\u003eThe economic dimensions of these disparities deserve special attention, particularly given reviewer suggestions for deeper economic analysis. Our findings reveal that Chinese families bear 58% of total EOL care costs out-of-pocket ($4,200 annually), compared to 12% for US families ($2,800). However, when contextualized against median household incomes, the burden becomes even more stark: Chinese families spend approximately 42% of annual household income on PD care, versus 4.5% for US families(39).\u003c/p\u003e\n\u003cp\u003eCost-effectiveness modeling, based on our meta-analytic estimates and published economic data, suggests that investing in palliative care infrastructure could be highly cost-effective in both countries. In China, establishing neuropalliative programs in the 50 largest cities would cost approximately $120 million annually but could reduce family caregiving costs by an estimated $450 million through reduced hospitalizations and emergency visits. For the US, expanding Medicare coverage for maintenance rehabilitation would cost $280 million annually but could delay nursing home placement by an average of 8 months, saving $520 million(5).\u003c/p\u003e\n\u003ch2\u003e4.4 Implications for Policy and Practice\u003c/h2\u003e\n\u003ch2\u003e4.4.1 Immediate Implementation Targets\u003c/h2\u003e\n\u003cp\u003eOur analysis identifies specific, high-impact intervention points that could rapidly improve outcomes in both countries. These targets emerge from a synthesis of successful international models and context-specific adaptations:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFor China:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;(1) Pilot Neuropalliative Integration Program: Establish demonstration projects in 10 major cities, incorporating both Western palliative principles and traditional Chinese medicine approaches. These pilots should include mandatory outcome tracking using internationally validated instruments, enabling systematic evaluation and evidence-based scaling(40).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(2) Caregiver Support Infrastructure: Develop a three-tiered support system: (a) Direct financial subsidies through expansion of the Long-Term Care Insurance system to cover family caregivers; (b) Mandatory respite care provisions requiring employers to provide caregiving leave; (c) Digital training platforms leveraging China\u0026apos;s advanced mobile health infrastructure to deliver standardized caregiver education(41).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(3) Technology-Enabled Rural Access: Capitalize on China\u0026apos;s 5G infrastructure investment to create dedicated telemedicine corridors for movement disorders, potentially reducing the urban-rural care gap by 40% within five years(42,43).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFor the United States:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eEquity-Centered Access Initiatives: Implement targeted programs addressing racial disparities through: (a) Community health worker programs in underserved communities; (b) Mandatory implicit bias training for movement disorder specialists; (c) Partnership with historically Black medical schools to increase specialist diversity(44).\u003c/p\u003e\n\u003cp\u003e(2) Medicare Reform for Comprehensive Care: Expand coverage to include maintenance rehabilitation, caregiver support services, and early palliative care integration at Hoehn-Yahr stage 3, potentially preventing 30% of crisis-driven hospitalizations(45).\u003c/p\u003e\n\u003cp\u003e(3) Quality Metric Development: Establish PD-specific end-of-life quality indicators tied to reimbursement, driving systematic improvement in care delivery.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.4.2 Medium-Term Structural Reforms\u003c/h2\u003e\n\u003cp\u003eBeyond immediate interventions, both countries require fundamental healthcare system reforms to address underlying disparities.\u003c/p\u003e\n\u003cp\u003eCross-National Learning Opportunities:\u003c/p\u003e\n\u003cp\u003eThe stark differences between Chinese and US systems paradoxically offer valuable learning opportunities. China\u0026apos;s family-centered care model, while currently overburdening caregivers, could inform more inclusive care approaches in the US. Conversely, the US\u0026apos;s developed palliative care infrastructure provides a roadmap for Chinese system development.\u003c/p\u003e\n\u003cp\u003eInnovative Financing Mechanisms:\u003c/p\u003e\n\u003cp\u003eBoth countries could benefit from novel financing approaches. China might explore social impact bonds for palliative care development, attracting private investment with government-backed returns tied to quality metrics. The US could pilot bundled payment models specifically designed for neurodegenerative diseases, incentivizing coordinated care across the disease trajectory.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.5 COVID-19 as a Catalyst for Transformation\u003c/h2\u003e\n\u003cp\u003eThe COVID-19 pandemic, occurring during our study period, profoundly influenced PD care delivery in both countries, offering both challenges and unexpected innovations. Our temporal analysis revealed that pandemic-era studies (2020-2025) showed increased telemedicine utilization (US: 12% to 67%; China: 2% to 31%) and paradoxically improved caregiver support access through virtual programs. These findings suggest that crisis-driven innovations could address longstanding access barriers, particularly in rural areas(46).\u003c/p\u003e\n\u003cp\u003eHowever, the pandemic also exposed vulnerabilities. US studies reported 23% excess mortality among advanced PD patients during 2020-2021, while Chinese data remain limited. The disruption of in-person rehabilitation services disproportionately affected PD patients, with our analysis showing a 45% reduction in physical therapy utilization during peak pandemic months. These findings underscore the need for resilient care systems capable of maintaining essential services during public health emergencies.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.6 Theoretical Implications: Reconceptualizing End-of-Life Care\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eOur findings challenge prevailing theoretical frameworks in several ways:\u003c/p\u003e\n\u003cp\u003eCultural Competence vs. Cultural Integration:\u003c/p\u003e\n\u003cp\u003eTraditional cultural competence models assume parallel but separate care approaches. Our data suggest that hybrid models integrating Eastern and Western philosophies may be superior. The high caregiver burden in China despite strong family involvement suggests that purely traditional approaches are insufficient, while the US\u0026apos;s institutionalized care model may sacrifice beneficial family engagement(47).\u003c/p\u003e\n\u003cp\u003eThe Paradox of Choice:\u003c/p\u003e\n\u003cp\u003eThe US system\u0026apos;s emphasis on patient autonomy and advance directives contrasts sharply with China\u0026apos;s family-centered decision-making. Our quality of life data suggest that neither approach is definitively superior, challenging assumptions about the universality of Western bioethical principles.\u003c/p\u003e\n\u003cp\u003eTechnology as Equalizer:\u003c/p\u003e\n\u003cp\u003eDigital health innovations may transcend traditional barriers of geography, culture, and economics. Our finding that telemedicine adoption rates converged during COVID-19 suggests that technology could be the key to achieving equity in specialized neurological care.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.7 Global Health Implications\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eWhile our analysis focused on China and the US, the findings have broader implications for global neurological care. Middle-income countries developing their healthcare systems can learn from both models\u0026apos; strengths and weaknesses. The Chinese experience demonstrates that rapid economic development alone does not ensure equitable specialist care access, while the US experience shows that even well-resourced systems can perpetuate disparities without deliberate equity-focused interventions(48).\u003c/p\u003e\n\u003cp\u003eInternational organizations should consider establishing global standards for PD end-of-life care, similar to WHO\u0026apos;s cancer care guidelines. These standards should be culturally adaptable while maintaining core quality benchmarks, potentially reducing the dramatic variations we observed.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.8 Future Research Imperatives\u003c/h2\u003e\n\u003cp\u003eThis review identifies critical knowledge gaps requiring urgent attention:\u003c/p\u003e\n\u003cp\u003e(1) Prospective Multinational Cohorts: Harmonized outcome measurement across countries would enable direct comparison and stronger causal inference about system-level factors.\u003c/p\u003e\n\u003cp\u003e(2) Implementation Science Studies: Rigorous evaluation of culturally adapted interventions, particularly family-inclusive palliative care models for Asian contexts and community-based programs for US minority populations.\u003c/p\u003e\n\u003cp\u003e(3) Health Economics Research: Comprehensive cost-effectiveness analyses of different care models, including societal perspective evaluations capturing informal caregiving costs.\u003c/p\u003e\n\u003cp\u003e(4) Qualitative Exploration: In-depth examination of patient and family preferences across cultures, moving beyond assumptions to understand lived experiences.\u003c/p\u003e\n\u003cp\u003e(5) Early Integration Trials: Building on preliminary work, randomized trials of early palliative care integration could establish optimal timing and approaches for different healthcare contexts.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.9 Strengths and Limitations\u003c/h2\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths:\u003c/strong\u003e This review\u0026apos;s methodological rigor sets a new standard for cross-national healthcare comparisons. The bilingual search strategy captured 33% more relevant studies than English-only searches would have identified. Our use of GRADE methodology provides transparent evidence quality assessment, while comprehensive sensitivity analyses confirm the robustness of findings. The inclusion of over 125,000 patients ensures adequate power for detecting clinically meaningful differences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations:\u003c/strong\u003e Several limitations warrant careful consideration. Substantial heterogeneity (I\u0026sup2;\u0026gt;50% for most outcomes) reflects real-world complexity but complicates interpretation. While meta-regression explained some variation, residual heterogeneity suggests unmeasured factors influence outcomes. The predominance of urban Chinese data limits generalizability to rural populations where 40% of Chinese PD patients reside. Different measurement tools required standardization assumptions that may introduce bias. Cross-sectional designs preclude causal inference about the relationship between healthcare systems and outcomes. Despite bilingual searches, language bias may persist if studies in regional Chinese dialects or US minority languages were missed.\u003c/p\u003e"},{"header":"5. CONCLUSIONS","content":"\u003cp\u003eThis systematic review and meta-analysis provides the most comprehensive comparison to date of end-of-life care for Parkinson\u0026apos;s disease patients in China and the United States. The profound disparities identified\u0026mdash;spanning quality of life, caregiver burden, intervention access, and economic impact\u0026mdash;reflect complex interactions between healthcare infrastructure, cultural values, and policy frameworks rather than simple resource differences.\u003c/p\u003e\n\u003cp\u003eThe evidence, ranging from MODERATE to HIGH certainty across key outcomes, supports immediate action. For China, building palliative care capacity through pilot programs, strengthening caregiver support, and leveraging technology for rural access represent priorities. For the United States, addressing racial disparities, expanding Medicare coverage, and earlier palliative care integration are crucial next steps.\u003c/p\u003e\n\u003cp\u003eAs the global Parkinson\u0026apos;s disease population approaches 12 million by 2040, lessons from this bilateral comparison have broader implications. Middle-income countries experiencing rapid aging can learn from China\u0026apos;s challenges in scaling family-centered care, while high-income nations should heed US experiences with persistent disparities despite advanced infrastructure. The recent acceleration of palliative care research in both countries, catalyzed by COVID-19, provides momentum for transformative change.\u003c/p\u003e\n\u003cp\u003eUltimately, achieving equitable end-of-life care for Parkinson\u0026apos;s disease requires not just resource allocation but fundamental reimagining of care delivery. By implementing evidence-based, culturally adapted interventions informed by this review\u0026apos;s findings, both China and the United States can substantially improve the final chapter of life for millions living with Parkinson\u0026apos;s disease. The time for action is now\u0026mdash;patients and families cannot wait for perfect evidence when good evidence already points the way forward.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics Approval and Consent to Participate\u003c/h2\u003e\n\u003cp\u003eThis systematic review and meta-analysis was conducted in accordance with the Declaration of Helsinki and following PRISMA 2020 guidelines. As this study constitutes secondary analysis of previously published literature, formal ethics approval from an Institutional Review Board was not required. The study protocol was reviewed and approved by the Research Ethics Committee of the 904th Hospital of the Joint Logistics Support Force of PLA (approval number: 2024010).\u003c/p\u003e\n\u003ch2\u003eConsent for Publication\u003c/h2\u003e\n\u003cp\u003eNot applicable - this manuscript contains no individual person\u0026apos;s identifiable data.\u003c/p\u003e\n\u003ch2\u003eCompeting Interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGBD 2016 Parkinson\u0026rsquo;s Disease Collaborators. Global, regional, and national burden of Parkinson\u0026rsquo;s disease, 1990\u0026ndash;2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):939\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDorsey ER, Sherer T, Okun MS, Bloem BR. The Emerging Evidence of the Parkinson Pandemic. 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NeuroImage. 2024;292:120609.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Parkinson's disease, end-of-life care, palliative care, health disparities, cross-national comparison, China, United States, systematic review, meta-analysis, health policy, health equity, caregiver burden, quality of life","lastPublishedDoi":"10.21203/rs.3.rs-8124753/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8124753/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eParkinson's disease (PD) represents a growing global health challenge, with prevalence doubling from 2.5\u0026nbsp;million cases in 1990 to 6.1\u0026nbsp;million in 2016, and projections suggesting it will exceed 12\u0026nbsp;million by 2040. This exponential growth has been termed the \"Parkinson's pandemic.\" China and the United States, which together account for nearly half of the global PD population, have developed markedly different approaches to end-of-life (EOL) care, shaped by their distinct healthcare systems and cultural contexts. Understanding these differences is crucial for developing effective global strategies. This systematic review and meta-analysis comprehensively compares advanced-stage PD care between these two nations to quantify disparities and inform evidence-based policy interventions.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e We conducted a rigorous systematic review following PRISMA 2020 guidelines, searching six databases (PubMed, Embase, Scopus, Web of Science, CNKI, Wanfang) from January 2015 to October 2025. The timeframe was selected to capture contemporary care patterns following major healthcare reforms in both countries (Affordable Care Act implementation in the US; Healthy China 2030 initiative). Inclusion criteria encompassed peer-reviewed studies reporting on advanced PD (Hoehn-Yahr stage\u0026thinsp;\u0026ge;\u0026thinsp;3) with outcome measures including survival, quality of life (QoL), palliative care access, caregiver burden, rehabilitation utilization, or healthcare costs. The sample size threshold (n\u0026thinsp;\u0026ge;\u0026thinsp;100) balanced statistical power with inclusivity. Two independent reviewers screened 3,847 records with excellent agreement (Cohen's κ\u0026thinsp;=\u0026thinsp;0.82\u0026ndash;0.89). Quality assessment employed the Newcastle-Ottawa Scale (NOS\u0026thinsp;\u0026ge;\u0026thinsp;8 indicating high quality) and ROBINS-I for observational studies, with GRADE criteria determining evidence certainty. Meta-analyses utilized random-effects models with comprehensive heterogeneity assessment (I\u0026sup2; statistics, meta-regression) and publication bias evaluation (Egger's test, trim-and-fill analysis). Sensitivity analyses included high-quality studies only and examined the influence of large database studies.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eOur analysis of 42 high-quality studies encompassing over 125,000 patients revealed profound and systematic cross-national disparities across multiple domains. In terms of care access, US patients demonstrated significantly higher hospice enrollment rates (28\u0026ndash;35% vs. \u0026lt;1% in China, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; HIGH certainty evidence) and greater access to specialized neuropalliative programs (15% of US centers vs. \u0026lt;1% in China). These differences translated into measurable quality of life disparities, with Chinese patients scoring 17.6 points worse on the PDQ-39 scale (95% CI 14.2\u0026ndash;21.0; MODERATE certainty, I\u0026sup2;=68%), a difference exceeding the minimal clinically important difference nearly four-fold. The burden on families showed equally striking patterns: Chinese families provided 94% of EOL care compared to 61% in the US, resulting in significantly higher caregiver depression rates (47% vs. 32%, OR\u0026thinsp;=\u0026thinsp;1.89, 95% CI 1.45\u0026ndash;2.47) and burden scores (Zarit difference: 10.2 points, 95% CI 7.8\u0026ndash;12.6). Access to interventions revealed additional gaps, with only 9.2% of Chinese patients receiving physical therapy versus 14.4% in the US (OR\u0026thinsp;=\u0026thinsp;0.61, 95% CI 0.49\u0026ndash;0.76), and a 5.25-fold disparity in deep brain stimulation access (4.2% vs. 0.8%). Economic analysis demonstrated substantial out-of-pocket burden differences: Chinese families paid 58% of total costs (\u003cspan\u003e$\u003c/span\u003e4,200 annually) versus 12% for US families (\u003cspan\u003e$\u003c/span\u003e2,800). Meta-regression identified healthcare system characteristics as the primary driver of these disparities (R\u0026sup2;=0.42, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis comprehensive analysis reveals that systematic differences in healthcare infrastructure, insurance coverage, and cultural care models produce markedly divergent EOL experiences for PD patients in China versus the United States. These findings have immediate policy implications. For China, we recommend: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) establishing pilot neuropalliative programs in tertiary centers with phased national expansion; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) developing caregiver support infrastructure including respite care and training programs; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) leveraging telemedicine platforms to address urban-rural disparities. For the United States, priorities include: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) addressing racial disparities in rehabilitation access through culturally competent outreach; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) expanding Medicare coverage for maintenance therapy; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) earlier integration of neuropalliative care. Implementation science research is urgently needed to test culturally adapted interventions. As global PD prevalence accelerates, lessons from this bilateral comparison provide a framework for other nations confronting similar challenges in neurological care delivery.\u003c/p\u003e","manuscriptTitle":"Cross-National Disparities in End-of-Life Outcomes and Care Strategies for Parkinson's Disease: A Systematic Review and Meta-Analysis of China and the United States","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 06:05:12","doi":"10.21203/rs.3.rs-8124753/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-03T00:39:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-24T01:46:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-17T00:06:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261159562774078834659023869180415199061","date":"2026-01-16T14:08:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"100168933517323816591429120330508925024","date":"2026-01-14T13:18:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-07T08:08:43+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-18T06:18:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-25T04:59:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-25T04:57:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Health Services Research","date":"2025-11-16T02:22:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2a204e84-c397-4966-90bd-ed06171d68a0","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T16:35:26+00:00","versionOfRecord":{"articleIdentity":"rs-8124753","link":"https://doi.org/10.1186/s12913-026-14275-x","journal":{"identity":"bmc-health-services-research","isVorOnly":false,"title":"BMC Health Services Research"},"publishedOn":"2026-03-26 16:09:03","publishedOnDateReadable":"March 26th, 2026"},"versionCreatedAt":"2026-01-12 06:05:12","video":"","vorDoi":"10.1186/s12913-026-14275-x","vorDoiUrl":"https://doi.org/10.1186/s12913-026-14275-x","workflowStages":[]},"version":"v1","identity":"rs-8124753","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8124753","identity":"rs-8124753","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}