Revealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas.

BACKGROUND: Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1-4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within the glioma environment remain poorly understood, and reliable prognostic markers remain elusive. Therefore, in-depth exploration of the tumor microenvironment (TME) and identification of predictive markers are crucial for improving the clinical management of glioma patients. RESULTS: Our analysis of single-cell RNA-sequencing data from glioma samples unveiled the immunosuppressive role of tumor-associated macrophages (TAMs), mediated through intricate interactions with tumor cells and lymphocytes. We also discovered the heterogeneity within TAMs, among which a group of suppressive TAMs named TAM-SPP1 demonstrated a significant association with Epidermal Growth Factor Receptor (EGFR) amplification, impaired T cell response and unfavourable patient survival outcomes. Furthermore, by leveraging genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes with a different constitution of TAMs, EGFR status and clinical outcomes were identified. Exploiting the molecular differences between these two subtypes, we developed a four-gene-based prognostic model. This model displayed strong associations with an elevated level of suppressive TAMs and could be used to predict anti-tumor immune response and prognosis in glioma patients. CONCLUSION: Our findings illuminated the molecular and cellular mechanisms that shape the immunosuppressive microenvironment in gliomas, providing novel insights into potential therapeutic targets. Furthermore, the developed prognostic model holds promise for predicting immunotherapy response and assisting in more precise risk stratification for glioma patients.

A review on trends in development and translation of omics signatures in cancer.

The field of cancer genomics and transcriptomics has evolved from targeted profiling to swift sequencing of individual tumor genome and transcriptome. The steady growth in genome, epigenome, and transcriptome datasets on a genome-wide scale has significantly increased our capability in capturing signatures that represent both the intrinsic and extrinsic biological features of tumors. These biological differences can help in precise molecular subtyping of cancer, predicting tumor progression, metastatic potential, and resistance to therapeutic agents. In this review, we summarized the current development of genomic, methylomic, transcriptomic, proteomic and metabolic signatures in the field of cancer research and highlighted their potentials in clinical applications to improve diagnosis, prognosis, and treatment decision in cancer patients.

The growing needs of genetic counselling-Feasibility in utilization of tele-genetic counselling in Asia and Hong Kong.

The need for the expansion of genomic services has been at a record time high in the past decade. As technological advancement continues to strengthen the entire genetic and genomic pipeline and clinical operational workflow, the major challenge remains to be the speed of workforce development to meet service growth. In particular, the international expansion of genetic counselling (GC) services has been a topic of interest for the past few years. GC is an emerging profession in most of Asia, and in many countries the profession of GC often refers to physicians or front-line health workers with expertise in genetics to provide GC services rather than being a specific independent profession. As genetic and genomic services, especially pre-test and post-test GC, expand globally, the need to tackle the longstanding obstacles of GC personnel shortage and funding issues must not be overlooked. There is an urgent need internationally, and especially in Asia, where GC profession is comparatively less well-established, to seek alternative approaches to meet service demand. The present review examines the global development and feasibility of tele-genetics and tele-genetic counselling (TGC), and serves as the foundation to explore a possible roadmap in Hong Kong via the Hong Kong Genome Project.

Meta-analysis of the diagnostic and clinical utility of exome and genome sequencing in pediatric and adult patients with rare diseases across diverse populations.

PURPOSE: This meta-analysis aims to compare the diagnostic and clinical utility of exome sequencing (ES) vs genome sequencing (GS) in pediatric and adult patients with rare diseases across diverse populations. METHODS: A meta-analysis was conducted to identify studies from 2011 to 2021. RESULTS: One hundred sixty-one studies across 31 countries/regions were eligible, featuring 50,417 probands of diverse populations. Diagnostic rates of ES (0.38, 95% CI 0.36-0.40) and GS (0.34, 95% CI 0.30-0.38) were similar (P = .1). Within-cohort comparison illustrated 1.2-times odds of diagnosis by GS over ES (95% CI 0.79-1.83, P = .38). GS studies discovered a higher range of novel genes than ES studies; yet, the rate of variant of unknown significance did not differ (P = .78). Among high-quality studies, clinical utility of GS (0.77, 95% CI 0.64-0.90) was higher than that of ES (0.44, 95% CI 0.30-0.58) (P < .01). CONCLUSION: This meta-analysis provides an important update to demonstrate the similar diagnostic rates between ES and GS and the higher clinical utility of GS over ES. With the newly published recommendations for clinical interpretation of variants found in noncoding regions of the genome and the trend of decreasing variant of unknown significance and GS cost, it is expected that GS will be more widely used in clinical settings.

Rare disease emerging as a global public health priority.

The genomics revolution over the past three decades has led to great strides in rare disease (RD) research, which presents a major shift in global policy landscape. While RDs are individually rare, there are common challenges and unmet medical and social needs experienced by the RD population globally. The various disabilities arising from RDs as well as diagnostic and treatment uncertainty were demonstrated to have detrimental influence on the health, psychosocial, and economic aspects of RD families. Despite the collective large number of patients and families affected by RDs internationally, the general lack of public awareness and expertise constraints have neglected and marginalized the RD population in health systems and in health- and social-care policies. The current Coronavirus Disease of 2019 (COVID-19) pandemic has exposed the long-standing and fundamental challenges of the RD population, and has reminded us of the critical need of addressing the systemic inequalities and widespread disparities across populations and jurisdictions. Owing to the commonality in goals between RD movements and universal health coverage targets, the United Nations (UN) has highlighted the importance of recognizing RDs in policies, and has recently adopted the UN Resolution to promote greater integration of RDs in the UN agenda, advancing UN's commitment in achieving the 2030 Sustainable Development Goals of "leav[ing] no one behind." Governments have also started to launch Genome Projects in their respective jurisdictions, aiming to integrate genomic medicine into mainstream healthcare. In this paper, we review the challenges experienced by the RD population, the establishment and adoption of RD policies, and the state of evidence in addressing these challenges from a global perspective. The Hong Kong Genome Project was illustrated as a case study to highlight the role of Genome Projects in enhancing clinical application of genomic medicine for personalized medicine and in improving equity of access and return in global genomics. Through reviewing what has been achieved to date, this paper will provide future directions as RD emerges as a global public health priority, in hopes of moving a step toward a more equitable and inclusive community for the RD population in times of pandemics and beyond.

DNA damage, DNA repair and carcinogenicity: Tobacco smoke versus electronic cigarette aerosol.

The allure of tobacco smoking is linked to the instant gratification provided by inhaled nicotine. Unfortunately, tobacco curing and burning generates many mutagens including more than 70 carcinogens. There are two types of mutagens and carcinogens in tobacco smoke (TS): direct DNA damaging carcinogens and procarcinogens, which require metabolic activation to become DNA damaging. Recent studies provide three new insights on TS-induced DNA damage. First, two major types of TS DNA damage are induced by direct carcinogen aldehydes, cyclic-1,N2-hydroxy-deoxyguanosine (γ-OH-PdG) and α-methyl-1, N2-γ-OH-PdG, rather than by the procarcinogens, polycyclic aromatic hydrocarbons and aromatic amines. Second, TS reduces DNA repair proteins and activity levels. TS aldehydes also prevent procarcinogen activation. Based on these findings, we propose that aldehydes are major sources of TS induce DNA damage and a driving force for carcinogenesis. E-cigarettes (E-cigs) are designed to deliver nicotine in an aerosol state, without burning tobacco. E-cigarette aerosols (ECAs) contain nicotine, propylene glycol and vegetable glycerin. ECAs induce O6-methyl-deoxyguanosines (O6-medG) and cyclic γ-hydroxy-1,N2--propano-dG (γ-OH-PdG) in mouse lung, heart and bladder tissues and causes a reduction of DNA repair proteins and activity in lungs. Nicotine and nicotine-derived nitrosamine ketone (NNK) induce the same types of DNA adducts and cause DNA repair inhibition in human cells. After long-term exposure, ECAs induce lung adenocarcinoma and bladder urothelial hyperplasia in mice. We propose that E-cig nicotine can be nitrosated in mouse and human cells becoming nitrosamines, thereby causing two carcinogenic effects, induction of DNA damage and inhibition of DNA repair, and that ECA is carcinogenic in mice. Thus, this article reviews the newest literature on DNA adducts and DNA repair inhibition induced by nicotine and ECAs in mice and cultured human cells, and provides insights into ECA carcinogenicity in mice.

Baseline knowledge and receptiveness to genetic testing for hereditary breast and ovarian cancer syndromes in Chinese high-risk females.

Limited studies have examined the pre-counselling knowledge and attitudes of high-risk women on hereditary breast and ovarian cancer (HBOC) syndromes genetic screening in Asia Pacific regions, particularly among Chinese. After controlling cost, an intrinsic barrier to undertake such screening, comprehensive understanding of the baseline characteristics of this cohort towards HBOC genetic counselling and testing service (GT) could be sought. This study aimed at exploring the baseline knowledge, possible motivators, barriers, and decisional factors of undertaking such service. One hundred and forty-two Southern Hong Kong Chinese high-risk females (89.4% with cancer history; 10.6% were cancer-free at-risk family members) completed a questionnaire right before their pre-testing GT. Results showed that perceived benefits to self and family members with reference to cancer prevention are important decisional motivators. A sponsored cancer genetic testing service in this cohort was crucial as 71.3% would not have opted for self-financed screening. Pre-testing and post-testing counselling were essential, particularly for older and less educated high-risk individuals. More importantly, after thorough pre-counselling with Q&A session, the entire cohort in this study gave written consent to undertake GT. Moreover, those proven to be germline pathogenic variant carriers were willing to share the information with family members and successfully persuaded them to pursue GT.

Health Financing Reforms for Moving towards Universal Health Coverage in the Western Pacific Region.

This article provides an overview of health financing reforms across countries in the Western Pacific Region as progress is made toward universal health coverage (UHC). Moving toward UHC requires a strong health system with sustainable financing, which countries strive to achieve through various approaches appropriate to their country contexts. Great efforts have been made by financing reforms through resource mobilization, risk pooling, resource allocation, and strategic purchasing. Overall governance of health financing systems has improved within the context of service delivery and budget reforms. But there are still challenges and ongoing needs to continue expanding health financing mechanisms equitably and efficiently, improving stewardship and accountability, strengthening the transition to domestic financing, and enabling evidence-informed priority setting and benefits design processes. Asian countries are rapidly developing and moving to more prepaid financing mechanisms with government subsidies to reduce relatively high out-of-pocket expenses, while facing implementation challenges in the governance and expansion of social health insurance. The Pacific island countries, on the other hand, face stagnating economic growth and rely on government financing, with some countries receiving significant external funding, making it important to have strong stewardship and public financing systems in place. The way forward calls for continuing to strengthen the evidence generation and monitoring function to assess country progress, reorienting primary health care as the foundation of the health sector to ensure that continuity of care is affordable and accountable, and leveraging the private sector to contribute to an equitable and efficient health system.

Correction: Assessing development assistance for child survival between 2000 and 2014: A multi-sectoral perspective.

[This corrects the article DOI: 10.1371/journal.pone.0178887.].

Assessing development assistance for child survival between 2000 and 2014: A multi-sectoral perspective.

BACKGROUND: The majority of Countdown countries did not reach the fourth Millennium Development Goal (MDG 4) on reducing child mortality, despite the fact that donor funding to the health sector has drastically increased. When tracking aid invested in child survival, previous studies have exclusively focused on aid targeting reproductive, maternal, newborn, and child health (RMNCH). We take a multi-sectoral approach and extend the estimation to the four sectors that determine child survival: health (RMNCH and non-RMNCH), education, water and sanitation, and food and humanitarian assistance (Food/HA). METHODS AND FINDINGS: Using donor reported data, obtained mainly from the OECD Creditor Reporting System and Development Assistance Committee, we tracked the level and trends of aid (in grants or loans) disbursed to each of the four sectors at the global, regional, and country levels. We performed detailed analyses on missing data and conducted imputation with various methods. To identify aid projects for RMNCH, we developed an identification strategy that combined keyword searches and manual coding. To quantify aid for RMNCH in projects with multiple purposes, we adopted an integrated approach and produced the lower and upper bounds of estimates for RMNCH, so as to avoid making assumptions or using weak evidence for allocation. We checked the sensitivity of trends to the estimation methods and compared our estimates to that produced by other studies. Our study yielded time-series and recipient-specific annual estimates of aid disbursed to each sector, as well as their lower- and upper-bounds in 134 countries between 2000 and 2014, with a specific focus on Countdown countries. We found that the upper-bound estimates of total aid disbursed to the four sectors in 134 countries rose from US$ 22.62 billion in 2000 to US$ 59.29 billion in 2014, with the increase occurring in all income groups and regions with sub-Saharan Africa receiving the largest sum. Aid to RMNCH has experienced the fastest growth (12.4%), followed by aid to Food/HA (9.4%), education (5.1%), and water and sanitation (5.0%). With the exception of RMNCH, the average per capita aid disbursed to each sector in the 74 Countdown countries was smaller than in non-Countdown countries. While countries with a large number of child deaths tend to receive the largest amount of disbursements, non-Countdown countries with small populations usually received the highest level of per capita aid for child survival among all 134 countries. Compared to other Countdown countries, those that met MDG 4 with a high reliance on health aid received much higher per capita aid across all sectors. These findings are robust to estimation methods. CONCLUSIONS: The study suggests that to improve child survival, better targeted investments should be made in the four sectors, and aid to non-health sectors could be a possible contributor to child mortality reduction. We recommend that future studies on tracking aid for child survival go beyond the health sector and include other sectors that directly affect child survival. Investigation should also be made about the link between aid to each of the four sectors and child mortality reduction.

Attitudes and compliance of clinical management after genetic testing for hereditary breast and ovarian cancer among high-risk Southern Chinese females with breast cancer history.

Western studies have shown that the uptake rates of surveillance and prophylaxis may vary among BRCA mutation carriers between ethnicities. The present study is the first to investigate the behavioural impact and subjective attitudes in Southern Chinese high-risk families who had undergone BRCA1 and BRCA2 genetic testing up to 2.5 years post-testing. Individuals who had such genetic testing and have consented to participate in the prospective database of Hong Kong Hereditary Breast Cancer Family Registry were recruited and surveyed by a face-to-face or telephone interview. Sociodemographic information, genetic test results, pre- and post-testing surveillance, medical regimes, and attitudes towards the choice of clinical management were obtained by interviews and retrieval of medical records using this prospective database. 69 females with breast cancer history were recruited into the study. Twenty-nine female carriers (15 BRCA1 mutated gene-carriers and 14 BRCA2 mutated gene-carriers) and 40 non-carriers of a BRCA 1/2 mutations were interviewed. The uptake rate of high risk breast screening i.e. clinical breast examination, mammography, and breast MRI is significantly higher among female carriers (48.3 %) after knowing genetic testing results than before (p < 0.01). A strong significant relationship between any increase or decrease of ovarian ultrasound screening (OS) and genetic status is found (p < .001), with more females did OS and with a higher frequency after knowing genetic testing results among both carriers (22.7 % â†’ 86.4 %) and non-carriers (37.5 % â†’ 50.0 %). Among carriers, very few opted for prophylactic surgeries. The present cohort might see prophylaxis as last resort and would use traditional Chinese medicine in cancer risk management.

Experience of Southern Chinese: new challenges in treating young female breast cancer patients at child-bearing age--a call for multi-disciplinary collaboration.

Compared with western populations, Southern Chinese, especially those residing in Hong Kong, are experiencing increasing breast cancer incidence and also a younger onset of breast cancer. Combating this problem and treating young women with breast cancer poses specific challenges and complicated considerations. With reference to the postponement in the age of marriage and reproduction in modern societies, the issue of fertility after breast cancer, especially for high-risk young patients, is one significant quality of life concern that cannot be underestimated as a secondary medical topic. While the issue has its significance and is confronting front-line breast cancer care teams of different disciplines, related research is mostly on Caucasians. In cultures where the traditional expectation on women for child-bearing is still prominent, young breast cancer patients may endure significant distress over fertility options after breast cancer. There is a lack of related data on Asian breast cancer survivors at child-bearing age, which calls for a pressing need to encourage qualitative groundwork, case reports, and cohort experiences in hope for providing insight and arouse research interest. In order to provide a long-term comprehensive multidisciplinary management service with encouragement to encompass prospects for a positive future among young breast cancer survivors, relevant disciplines need to collaborate and work efficaciously together both on clinical and research aspects of cancer-related fertility issues.

What made her give up her breasts: a qualitative study on decisional considerations for contralateral prophylactic mastectomy among breast cancer survivors undergoing BRCA1/2 genetic testing.

OBJECTIVE: This qualitative study retrospectively examined the experience and psychological impact of contralateral prophylactic mastectomy (CPM) among Southern Chinese females with unilateral breast cancer history who underwent BRCA1/2 genetic testing. Limited knowledge is available on this topic especially among Asians; therefore, the aim of this study was to acquire insight from Chinese females' subjective perspectives. METHODS: A total of 12 semi-structured in-depth interviews, with 11 female BRCA1/BRCA 2 mutated gene carriers and 1 non-carrier with a history of one-sided breast cancer and genetic testing performed by the Hong Kong Hereditary Breast Cancer Family Registry, who subsequently underwent CPM, were assessed using thematic analysis and a Stage Conceptual Model. Breast cancer history, procedures conducted, cosmetic satisfaction, pain, body image and sexuality issues, and cancer risk perception were discussed. Retrieval of medical records using a prospective database was also performed. RESULTS: All participants opted for prophylaxis due to their reservations concerning the efficacy of surveillance and worries of recurrent breast cancer risk. Most participants were satisfied with the overall results and their decision. One-fourth expressed different extents of regrets. Psychological relief and decreased breast cancer risk were stated as major benefits. Spouses' reactions and support were crucial for post-surgery sexual satisfaction and long-term adjustment. CONCLUSIONS: Our findings indicate that thorough education on cancer risk and realistic expectations of surgery outcomes are crucial for positive adjustment after CPM. Appropriate genetic counseling and pre-and post-surgery psychological counseling were necessary. This study adds valuable contextual insights into the experiences of living with breast cancer fear and the importance of involving spouses when counseling these patients.

Hope-based intervention for individuals susceptible to colorectal cancer: a pilot study.

Individuals undergoing genetic testing for hereditary colorectal cancer (HCRC) are prone to develop psychological problems. This study investigated the short-term efficacy of a hope-based intervention program in increasing hope levels and decreasing psychopathology among HCRC genetic testing recipients. A longitudinal study was carried out on HCRC genetic testing recipients recruited by the Hereditary Gastrointestinal Cancer Registry. Participants joined a hope-based intervention program consisting of six sessions of weekly closed group therapy. Psychological questionnaires were administered immediately before the first and after the last sessions of the program measuring hope, anxiety and depression levels of the participants. There were 22 participants (7 men and 15 women) at a mean age of 49.4 ± 9.6 years. Women tended to have higher level of anxiety than men at pre-intervention. Paired sample t tests were conducted. Hope levels increased significantly from pre- to post-intervention (pre-total hope score = 5.56; post-total hope score = 6.07; t(1) = -0.281, p < 0.05). Anxiety level also decreased significantly from pre- to post-intervention (pre-anxiety score = 7.38; post-anxiety score = 5.90; t (1) = 2.35, p < 0.05). Our findings imply that hope-based intervention program would be effective in enhancing hope in HCRC genetic testing recipients. The program may also be more effective in alleviating anxiety than depression in these individuals.

Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study.

BACKGROUND: Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. METHODS: A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer Registry to determine psychological outcomes after genetic testing. Self-completed questionnaires were administered immediately before (pre-disclosure baseline) and 2 weeks, 4 months and 1 year after result disclosure. Using validated psychological inventories, the cognitive style of hope was measured at baseline, and the psychological distress of depression and anxiety was measured at all time points. RESULTS: Of the 76 participating subjects, 71 individuals (43 men and 28 women; mean age 38.9 +/- 9.2 years) from nine FAP and 24 HNPCC families completed the study, including 39 mutated gene carriers. Four patterns of outcome trajectories were created using established norms for the specified outcome measures of depression and anxiety. These included chronic dysfunction (13% and 8.7%), recovery (0% and 4.3%), delayed dysfunction (13% and 15.9%) and resilience (76.8% and 66.7%). Two logistic regression analyses were conducted using hope at baseline to predict resilience, with depression and anxiety employed as outcome indicators. Because of the small number of participants, the chronic dysfunction and delayed dysfunction groups were combined into a non-resilient group for comparison with the resilient group in all subsequent analysis. Because of low frequencies, participants exhibiting a recovery trajectory (n = 3 for anxiety and n = 0 for depression) were excluded from further analysis. Both regression equations were significant. Baseline hope was a significant predictor of a resilience outcome trajectory for depression (B = -0.24, p < 0.01 for depression); and anxiety (B = -0.11, p = 0.05 for anxiety). CONCLUSIONS: The current findings suggest that hopefulness may predict resilience after HCRC genetic testing in Hong Kong Chinese. Interventions to increase the level of hope may be beneficial to the psychological adjustment of CRC genetic testing recipients.

SOCR Analyses: Implementation and Demonstration of a New Graphical Statistics Educational Toolkit.

The web-based, Java-written SOCR (Statistical Online Computational Resource) tools have been utilized in many undergraduate and graduate level statistics courses for seven years now (Dinov 2006; Dinov et al. 2008b). It has been proven that these resources can successfully improve students' learning (Dinov et al. 2008b). Being first published online in 2005, SOCR Analyses is a somewhat new component and it concentrate on data modeling for both parametric and non-parametric data analyses with graphical model diagnostics. One of the main purposes of SOCR Analyses is to facilitate statistical learning for high school and undergraduate students. As we have already implemented SOCR Distributions and Experiments, SOCR Analyses and Charts fulfill the rest of a standard statistics curricula. Currently, there are four core components of SOCR Analyses. Linear models included in SOCR Analyses are simple linear regression, multiple linear regression, one-way and two-way ANOVA. Tests for sample comparisons include t-test in the parametric category. Some examples of SOCR Analyses' in the non-parametric category are Wilcoxon rank sum test, Kruskal-Wallis test, Friedman's test, Kolmogorov-Smirnoff test and Fligner-Killeen test. Hypothesis testing models include contingency table, Friedman's test and Fisher's exact test. The last component of Analyses is a utility for computing sample sizes for normal distribution. In this article, we present the design framework, computational implementation and the utilization of SOCR Analyses.

SOCR Analyses - an Instructional Java Web-based Statistical Analysis Toolkit.

The Statistical Online Computational Resource (SOCR) designs web-based tools for educational use in a variety of undergraduate courses (Dinov 2006). Several studies have demonstrated that these resources significantly improve students' motivation and learning experiences (Dinov et al. 2008). SOCR Analyses is a new component that concentrates on data modeling and analysis using parametric and non-parametric techniques supported with graphical model diagnostics. Currently implemented analyses include commonly used models in undergraduate statistics courses like linear models (Simple Linear Regression, Multiple Linear Regression, One-Way and Two-Way ANOVA). In addition, we implemented tests for sample comparisons, such as t-test in the parametric category; and Wilcoxon rank sum test, Kruskal-Wallis test, Friedman's test, in the non-parametric category. SOCR Analyses also include several hypothesis test models, such as Contingency tables, Friedman's test and Fisher's exact test.The code itself is open source (http://socr.googlecode.com/), hoping to contribute to the efforts of the statistical computing community. The code includes functionality for each specific analysis model and it has general utilities that can be applied in various statistical computing tasks. For example, concrete methods with API (Application Programming Interface) have been implemented in statistical summary, least square solutions of general linear models, rank calculations, etc. HTML interfaces, tutorials, source code, activities, and data are freely available via the web (www.SOCR.ucla.edu). Code examples for developers and demos for educators are provided on the SOCR Wiki website.In this article, the pedagogical utilization of the SOCR Analyses is discussed, as well as the underlying design framework. As the SOCR project is on-going and more functions and tools are being added to it, these resources are constantly improved. The reader is strongly encouraged to check the SOCR site for most updated information and newly added models.

Preliminary study into the economic burden of Down syndrome in China.

BACKGROUND: To measure the economic burden of Down syndrome (DS) in China is to facilitate strategic planning development for managing and preventing DS. METHODS: The economic burden of DS was calculated from direct healthcare costs, direct non-health-care costs, and indirect costs. The incidence approach was employed to measure the lifetime economic burden of a new DS birth in China in 2003. Most parameters came from a household health services survey, which was given to caregivers of people with DS. This survey was conducted in Hebei, Shaanxi, and Shanghai in 2004. RESULTS: Caregivers of 222 people with DS were interviewed in six cities and neighboring rural areas. Average expenses and utilization rate of different services by age groups from this sample were obtained to estimate the economic burden of DS. The average lifetime economic burden of a new DS case from the family perspective and the societal perspective amounted to US$47,000 and US$55,000, respectively. Indirect (productivity) costs were responsible for most of the total economic loss. Sensitivity analysis showed that the incidence rate, survival rate, value of productivity such as GDP per capita or salary, productivity of people with DS, and utilization rate of related services were influencing factors to the economic burden of DS. CONCLUSIONS: The economic burden of DS is substantial for the family of a person with DS, as well as to society. Appropriate management and prevention of DS is needed to reduce the heavy burden for people with DS and their families. Birth Defects Research (Part A) 2008.

Cost-effectiveness analysis of prenatal diagnosis intervention for Down's syndrome in China.

OBJECTIVES: The cost-effectiveness of prenatal diagnosis intervention for Down's syndrome (DS) in China was assessed and evidence-based information for policy makers and providers is presented. METHODS: Based on field surveys in four selected cities in China and a literature review, the economic evaluation of prenatal diagnosis for DS from a societal perspective is conducted by cost-effectiveness analysis. RESULTS: In current clinical practice, for a cohort of 10,000 pregnant women, the strategy that delivers karyotyping by chorionic villus sampling (CVS) or amniocentesis (AC) only to those pregnant women 35 years of age and older (maternal age screening strategy) can detect .67 DS births. The strategy that offers the diagnostic test after maternal serum screening with alpha-fetoprotein and human chorionic gonadotrophin (maternal serum screening strategy) can detect 1.41 DS births. The cost per prevented DS birth by the maternal age screening strategy and maternal serum screening strategy is US$ 13,091 and US$ 56,048, respectively. Sensitivity analysis shows that the maternal serum screening strategy can be cost-effective if uptake rate of CVS or AC for patients with positive serum tests increase while the cost of serum screening decreases. CONCLUSIONS: Although, in general, serum screening has been found to be more cost-effective than maternal age screening, this appears not to be the case in China. The reasons appear to be low uptake rate of the maternal serum strategy, low uptake rate of CVS or AC, and the high price of serum screening. Our findings are that health system factors concerning technology utilization are important determinants of the technology's efficiency.