BackgroundResponsiveness of health care services in low and middle income countries has been given little attention. Despite being introduced over a decade ago in many developing countries, national health insurance schemes have yet to be evaluated in terms of responsiveness of health care services. Although this responsiveness has been evaluated in many developed countries, it has rarely been done in developing countries. The concept of responsiveness is multi-dimensional and can be measured across various domains including prompt attention, dignity, communication, autonomy, choice of provider, quality of facilities, confidentiality and access to family support. This study examines the insured users’ perspectives of their health care services’ responsiveness.MethodsThis retrospective, cross-sectional survey took place between October 2010 and March 2011. The study used a modified out-patient questionnaire from a responsiveness survey designed by the World Health Organization (WHO). Seven hundred and ninety six (796) enrolees, insured for more than one year in Kaduna State-Nigeria, were interviewed. Generalized ordered logistic regression was used to identify factors that influenced the users’ perspectives on responsiveness to health services and quantify their effects.ResultsCommunication (55.4%), dignity (54.1%), and quality of facilities (52.0%) were rated as “extremely important” responsiveness domains. Users were particularly contented with quality of facilities (42.8%), dignity (42.3%), and choice of provider (40.7%). Enrolees indicated lower contentment on all other domains. Type of facility, gender, referral, duration of enrolment, educational status, income level, and type of marital status were most related with responsiveness domains.ConclusionsAssessing the responsiveness of health care services within the NHIS is valuable in investigating the scheme’s implementation. The domains of autonomy, communication and prompt attention were identified as priority areas for action to improve this responsiveness. For the Nigerian context, we suggest that health care providers in the NHIS should pay attention to these domains, and the associated characteristics of users, when delivering health care services to their clients. Policy makers, and the insurance regulatory agency, should consider the reform strategies of monitoring and quality assurance which focus on the domains of responsiveness to lessen the gap between users’ expectations and their experiences with health services.
To identify new tumor-suppressor gene candidates relevant for human hepatocarcinogenesis, we performed genome-wide methylation profiling and vertical integration with arraybased comparative genomic hybridization (aCGH), as well as expression data from a cohort of well-characterized human hepatocellular carcinomas (HCCs). Bisulfite-converted DNAs from 63 HCCs and 10 healthy control livers were analyzed for the methylation status of more than 14,000 genes. After defining the differentially methylated genes in HCCs, we integrated their DNA copy-number alterations as determined by aCGH data and correlated them with gene expression to identify genes potentially silenced by promoter hypermethylation. Aberrant methylation of candidates was further confirmed by pyrosequencing, and methylation dependency of silencing was determined by 5-aza-2 0 -deoxycytidine (5-aza-dC) treatment. Methylation profiling revealed 2,226 CpG sites that showed methylation differences between healthy control livers and HCCs. Of these, 537 CpG sites were hypermethylated in the tumor DNA, whereas 1,689 sites showed promoter hypomethylation. The hypermethylated set was enriched for genes known to be inactivated by the polycomb repressive complex 2, whereas the group of hypomethylated genes was enriched for imprinted genes. We identified three genes matching all of our selection criteria for a tumor-suppressor gene (period homolog 3 [PER3], insulin-like growth-factor-binding protein, acid labile subunit [IGFALS], and protein Z). PER3 was down-regulated in human HCCs, compared to peritumorous and healthy liver tissues. 5-aza-dC treatment restored PER3 expression in HCC cell lines, indicating that promoter hypermethylation was indeed responsible for gene silencing. Additionally, functional analysis supported a tumor-suppressive function for PER3 and IGFALS in vitro. Conclusion: The present study illustrates that vertical integration of methylation data with high-resolution genomic and transcriptomic data facilitates the identification of new tumor-suppressor gene candidates in human HCC. (HEPATOLOGY 2012;56:1817-1827 H epatocellular carcinoma (HCC) is the fifthmost frequent cancer worldwide and has a poor prognosis. 1 Various etiologies have been linked to HCC development, most of which cause chronic liver damage and finally lead to liver cirrhosis.The most prevalent etiological factors are chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, chronic alcohol consumption, and, in certain geographical areas, aflatoxin B1 food contamination. 2 Approximately 10% of HCC patients lack viral
The Human Genome Project and the ensuing International HapMap Project were largely motivated by human health issues. But the distance from a DNA sequence variation to a novel disease gene is considerable; for complex diseases, closing this gap hinges on the premise that they arise mainly from heritable causes. Using cancer as an example of complex disease, we examine the scientific evidence for the hypothesis that human diseases result from interactions between genetic variants and the environment.
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