Publications
49 results found
Zhu F, Loh M, Hill J, et al., 2009, Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort study, BMC Gastroenterology, Vol: 9, ISSN: 1471-230X
BACKGROUND: Intestinal metaplasia (IM) is an important precursor lesion in the development of gastric cancer (GC). The aim of this study was to investigate genetic factors previously linked to GC risk for their possible association with IM. A total of 18 polymorphisms in 14 candidate genes were evaluated in a Singapore-Chinese population at high risk of developing GC. METHODS: Genotype frequencies were compared between individuals presenting with (n = 128) or without (n = 246) IM by both univariate and multivariate analysis. RESULTS: Carriers of the NQO1 609 T allele showed an association with IM in individuals who were seropositive for Helicobacter pylori (HP+; OR = 2.61, 95%CI: 1.18-5.80, P = .018). The IL-10 819 C allele was also associated with IM in HP+ individuals (OR = 2.32, 95%CI: 1.21-4.43, P = 0.011), while the PTPN11 A allele was associated with IM in HP- individuals (OR = 2.51, 95%CI: 1.16-5.40, P = 0.019), but showed an inverse association in HP+ subjects (OR = 0.46, 95%CI: 0.21-0.99, P = 0.048). CONCLUSION: Polymorphisms in NQO1, IL-10 and PTPN11, in combination with HP status, could be used to identify individuals who are more likely to develop IM and therefore GC.
Loh M, Koh KX, Yeo BH, et al., 2009, Meta-analysis of genetic polymorphisms and gastric cancer risk: variability in associations according to race., Eur J Cancer, Vol: 45, Pages: 2562-2568
The goal of this study was to consolidate information on genetic risk factors for gastric cancer. An additional aim was to investigate the influence of race on these genetic risk associations. Relevant studies were identified from PubMed and references of retrieved articles. Meta-analysis techniques were used to summarise associations between genetic polymorphisms and gastric cancer. A total of 203 relevant studies were identified, assessing 225 polymorphisms across 95 genes. Subgroup analysis indicated that Chinese, Japanese and Korean data were consistent and could be pooled. However, 6 of 13 polymorphisms (ACE I/D, CCND1 870G>A, CDH1 -160C>A, IL1B -511C>T, IL4 -590C>T, IL10 -592A>C) displayed conflicting effects between Asian and Caucasian populations, three of which (ACE I/D, CCND1 870G>A, IL1B -511C>T) had significantly different odds ratios between the two racial groups. In total, 37 polymorphisms across 27 genes were found to be significantly associated with gastric cancer in Asians, and 12 polymorphisms across 11 genes in Caucasians. Consolidated panels of polymorphisms associated with gastric cancer risk were identified in Asians and Caucasians. The results caution against the assumption that genetic risk factors are consistent between races.
SiekierkaHarreis M, Kuhr N, Willers R, et al., 2009, Impact of genetic polymorphisms of the renin–angiotensin system and of non‐genetic factors on kidney transplant function – a single‐center experience, Clinical Transplantation, Vol: 23, Pages: 606-615, ISSN: 0902-0063
<jats:p><jats:bold>Abstract: </jats:bold> Renin–angiotensin–aldosterone system (RAAS) polymorphisms such as the angiotensinogen‐gene‐M235T‐, the angiotensin‐conversion enzyme (ACE)‐gene I/D‐ and the angiotensin‐II‐type 1‐receptor‐(AT<jats:sub>1</jats:sub>R)‐A1166C‐polymorphism have been implicated in renal insufficiency and hypertension. We studied the association of these RAAS genotypes and non‐genetic factors with transplant function and hypertension after renal graft transplantation (NTX). A total of 229 renal graft recipients, transplanted at a single center, were monitored up to 54 months and genotyped using polymerase chain reaction. The prevalence of the genotypes was comparable to a control group of healthy volunteers. Genotype and clinical outcome was analyzed using <jats:sc>anova</jats:sc>, while the <jats:italic>k</jats:italic>‐nearest neighbor method was used for a pattern recognition analysis of the complete database. Hypertension after NTX was not influenced by the RAAS polymorphisms. The DD‐genotype of the ACE‐I/D‐polymorphism was associated with significantly deteriorated renal transplant function during the months 18 to 30 after transplantation according to <jats:sc>anova</jats:sc> at p < 0.05, as were non‐genetic factors like long hospitalization, poor primary transplant function, and frequent rejections. Pattern recognition identified, the use of cyclosporine (odds ratio of 4.25) and the use of Ang II‐receptor‐blockers at discharge indicating the need of effective antihypertensive treatment (odds ratio of 3.26) as risk factors for transplant function loss. Altogether, the significant impact of the DD‐genotype on the outcome after renal transplantation emphasizes the early identification of RAAS genotypes.</jats:p>
Chong P, Lee H, Kong JW, et al., 2008, Phosphoproteomics, oncogenic signaling and cancer research, PROTEOMICS, Vol: 8, Pages: 4370-4382, ISSN: 1615-9853
<jats:title>Abstract</jats:title><jats:p>The past 5 years have seen an explosion of phosphoproteomics methods development. In this review, using epidermal growth‐factor signaling as a model, we will discuss how phosphoproteomics, along with bioinformatics and computational modeling, have impacted key aspects of oncogenic signaling such as in the temporal fine mapping of phosphorylation events, and the identification of novel tyrosine kinase substrates and phosphorylation sites. We submit that the next decade will see considerable exploitation of phosphoproteomics in cancer research. Such a phenomenon is already happening as exemplified by its use in promoting the understanding of the molecular etiology of cancer and target‐directed therapeutics.</jats:p>
Wong W-C, Loh M, Eisenhaber F, 2008, On the necessity of different statistical treatment for Illumina BeadChip and Affymetrix GeneChip data and its significance for biological interpretation., Biol Direct, Vol: 3
BACKGROUND: The original spotted array technology with competitive hybridization of two experimental samples and measuring relative expression levels is increasingly displaced by more accurate platforms that allow determining absolute expression values for a single sample (for example, Affymetrix GeneChip and Illumina BeadChip). Unfortunately, cross-platform comparisons show a disappointingly low concordance between lists of regulated genes between the latter two platforms. RESULTS: Whereas expression values determined with a single Affymetrix GeneChip represent single measurements, the expression results obtained with Illumina BeadChip are essentially statistical means from several dozens of identical probes. In the case of multiple technical replicates, the data require, therefore, different stistical treatment depending on the platform. The key is the computation of the squared standard deviation within replicates in the case of the Illumina data as weighted mean of the square of the standard deviations of the individual experiments. With an Illumina spike experiment, we demonstrate dramatically improved significance of spiked genes over all relevant concentration ranges. The re-evaluation of two published Illumina datasets (membrane type-1 matrix metalloproteinase expression in mammary epithelial cells by Golubkov et al. Cancer Research (2006) 66, 10460; spermatogenesis in normal and teratozoospermic men, Platts et al. Human Molecular Genetics (2007) 16, 763) significantly identified more biologically relevant genes as transcriptionally regulated targets and, thus, additional biological pathways involved. CONCLUSION: The results in this work show that it is important to process Illumina BeadChip data in a modified statistical procedure and to compute the standard deviation in experiments with technical replicates from the standard errors of individual BeadChips. This change leads also to an improved concordance with Affymetrix GeneChip results as the spermatogen
Tan S-H, Ida H, Lau Q-C, et al., 2007, Detection of promoter hypermethylation in serum samples of cancer patients by methylation-specific polymerase chain reaction for tumour suppressor genes including RUNX3., Oncol Rep, Vol: 18, Pages: 1225-1230, ISSN: 1021-335X
The purpose was to validate the use of RUNX3 as a potential biomarker for detection of cancer in serum samples and to determine its sensitivity alone and in combination with p16, RASSF1A and CDH1 using methylation-specific polymerase chain reaction (MSP). We examined the promoter methylation status of RUNX3, p16, RASSF1A and CDH1 by MSP using the serum of 70 metastatic breast, non-small cell lung, gastric, pancreatic, colorectal or hepatocellular carcinomas. The DNA from 10 healthy serum controls was used to determine the specificity of methylation. According to our results, promoter hyper-methylation of RUNX3 was detected in the serum of 44 patients comprising breast 9/19 (47%), non-small cell lung 11/20 (55%), gastric 4/4 (100%), pancreatic 2/2 (100%), colorectal 11/17 (65%) and liver 7/8 (88%) carcinomas. Comparative figures for the other genes were as follows: p16 - 39/70 (7/19, 10/20, 2/4, 0/2, 12/17, 8/8); RASSF1A - 24/70 (8/19, 6/20, 1/4, 1/2, 4/17, 4/8); CDH1 - 10/70 (0/19, 4/20, 1/4, 1/2, 3/17, 1/8). Using a panel of four genes, hypermethylation of one or more genes was found in 62/70 samples (15/19, 19/20, 4/4, 2/2, 14/17, 8/8). A panel of three genes omitting RUNX3 detected hyper-methylation in only 50/70 samples. No methylation was detected in the 10 healthy serum controls. Thus, RUNX3 can be detected in the serum of a high proportion of advanced cancers. This suggests that serum hypermethylation of RUNX3 is at least as, or possibly more sensitive a marker, than other tumor suppressor genes currently under investigation. Inclusion of RUNX3 in gene panels can potentially increase the sensitivity of such panels for serum diagnosis of malignancies and warrants further study.
Loh M, Tan CH, Sim K, et al., 2007, Epidemiology of completed suicides in Singapore for 2001 and 2002., Crisis, Vol: 28, Pages: 148-155, ISSN: 0227-5910
This study provides an analysis of 640 completed suicide cases in Singapore for the years 2001 and 2002, compared to previous years and in relation to demographic and socioeconomic factors, as well as to the characteristics of a subgroup of suicide victims with prior psychiatric illness. There was little change in the suicide pattern over the 2 years studied compared to previous years. The sex ratio was constant at 1.5. Population-adjusted ratios were 1 for Chinese, 0.5 for Malays, and >1 for both Indians and other ethnic groups. Falling from heights ranked first in terms of method adopted for both years. A disproportionately higher number of suicides were recorded for the 25-34 and the > or =75-year-old age groups. A total of 47 (17.2%) in 2001 and 74 (20.2%) in 2002 of the cases had a history of prior psychiatric illness, with psychotic disorders being the most common diagnostic category. There was also a statistically significant correlation between unemployment and incidence rates. Although the overall rate of elderly suicides had gone down since the 1990s, prevention strategy should focus on the elderly as this rate is still about 3-4 times the national average.
Mondry A, Loh M, Laurence KB, et al., 2006, DNA polymorphisms and renal disease: a critical appraisal of studies presented at the annual ERA/EDTA and ASN conferences in 2004 and 2005., Nephrol Dial Transplant, Vol: 21, Pages: 2775-2779, ISSN: 0931-0509
Countless studies try to associate single DNA polymorphisms with disease, while there is growing evidence that many of these studies are of flawed design. Based on the Journal of the American Society of Nephrology (JASN) requirements for gene-disease association study quality, the abstracts presented at the two major international nephrology conferences in 2004 and 2005 organized by the European Renal Association/European Dialysis and Transplantation Association (ERA/EDTA) and American Society of Nephrology (ASN) are analysed to show how this problem affects nephrology. Over time, average sample numbers have increased, as have the numbers of abstracts compliant with the JASN requirements. This indicates a potential beneficial effect of the published stricter guidelines on study quality. Alternative options include pre-registration of studies in dedicated databases, secondary assessment of association studies through meta-analysis and participation in network approaches, such as the Human Genome Epidemiology Network (HuGE Net) and the Renal Genome Network.
Lau QC, Raja E, Salto-Tellez M, et al., 2006, RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer., Cancer Res, Vol: 66, Pages: 6512-6520, ISSN: 0008-5472
A tumor suppressor function has been attributed to RUNX3, a member of the RUNX family of transcription factors. Here, we examined alterations in the expression of three members, RUNX1, RUNX2, and RUNX3, and their interacting partner, CBF-beta, in breast cancer. Among them, RUNX3 was consistently underexpressed in breast cancer cell lines and primary tumors. Fifty percent of the breast cancer cell lines (n = 19) showed hypermethylation at the promoter region and displayed significantly lower levels of RUNX3 mRNA expression (P < 0.0001) and protein (P < 0.001). In primary Singaporean breast cancers, 9 of 44 specimens showed undetectable levels of RUNX3 by immunohistochemistry. In 35 of 44 tumors, however, low levels of RUNX3 protein were present. Remarkably, in each case, protein was mislocalized to the cytoplasm. In primary tumors, hypermethylation of RUNX3 was observed in 23 of 44 cases (52%) and was undetectable in matched adjacent normal breast epithelium. Mislocalization of the protein, with or without methylation, seems to account for RUNX3 inactivation in the vast majority of the tumors. In in vitro and in vivo assays, RUNX3 behaved as a growth suppressor in breast cancer cells. Stable expression of RUNX3 in MDA-MB-231 breast cancer cells led to a more cuboidal phenotype, significantly reduced invasiveness in Matrigel invasion assays, and suppressed tumor formation in immunodeficient mice. This study provides biological and mechanistic insights into RUNX3 as the key member of the family that plays a role in breast cancer. Frequent protein mislocalization and methylation could render RUNX3 a valuable marker for early detection and risk assessment.
Liang X, Lau QC, Salto-Tellez M, et al., 2006, Mutational hotspot in exon 20 of PIK3CA in breast cancer among Singapore Chinese., Cancer Biol Ther, Vol: 5, Pages: 544-548, ISSN: 1538-4047
The recent identification of somatic mutations in the catalytic region of PIK3 (PIK3CA) in breast cancer and demonstration of their oncogenic function has implicated PIK3CA in mammary carcinogenesis. To investigate possible ethnic differences in patterns of PIK3CA mutations in Singaporean Chinese breast cancer and to characterize these in a panel of cell lines, we sequenced exons 9 and 20 in 80 primary tumors, 19 breast cancer cell lines and 7 normal human mammary epithelial cells (HMECs). Searching for novel hotspots of mutation, we sequenced additional exons (1, 2, 6, 7, 14 and 18) in 20 primary tumors and 6 breast cancer cell lines. We detected 33 point mutations in 31 of 80 (39%) breast cancers, and 11 mutations in 10 of 19 (53%) breast cancer cell lines. No mutations were detected in normal breast tissue adjacent to the tumor, or in the 6 normal HMECs. The exon 20 A3140G (H1047R) substitution was identified most frequently (22/31, 71%) and showed a significant association with patient age (p = 0.043) and stage of the disease (p = 0.025), but not with ER/PR status or histological grade of the tumor. The incidence of point mutations in PIK3CA, the A3140G substitution in particular, in Singapore breast cancers are among the most frequent reported to date for any gene in breast cancer. The results suggest that mutation of PIK3CA might contribute to development of early stage breast cancer and could provide a potent target for early diagnosis and therapy.
Tan E-C, Loh M, Chuon D, et al., 2006, Singapore Human Mutation/Polymorphism Database: a country-specific database for mutations and polymorphisms in inherited disorders and candidate gene association studies., Hum Mutat, Vol: 27, Pages: 232-235
There is a need for country/population-specific databases because the existence of population-specific mutations for single gene disorders is well documented, and there is also good evidence for ethnic differences in the frequencies of genetic variations involved in complex disorders. Thus the Singapore Human Mutation/Polymorphism Database (SHMPD) was created to provide clinicians and scientists access to a central genetic database for the Singapore population. The data catalogued in the database include mutations identified in Singapore for Mendelian diseases, and frequencies of polymorphisms that have been investigated in either healthy controls or samples associated with specific phenotypes. Data from journal articles identified by searches in PubMed and other online resources, and via personal communications with researchers were compiled and assembled into a single database. Genes are categorized alphabetically and are also searchable by name and disease. The information provided for each variant of the gene includes the protein encoded, phenotype association, gender, size, and ethnic origin of the sample, as well as the reported genotype and allele frequencies, and direct links to the corresponding abstracts on PubMed. Our database will facilitate molecular diagnosis of Mendelian disorders and improve study designs for complex traits. It will be useful not only for researchers in Singapore, but also for those in countries with similar ethnic backgrounds, such as China, Taiwan, Hong Kong, Indonesia, and Malaysia.
Tan S-H, Ida H, Goh B-C, et al., 2006, Analyses of promoter hypermethylation for RUNX3 and other tumor suppressor genes in nasopharyngeal carcinoma., Anticancer Res, Vol: 26, Pages: 4287-4292, ISSN: 0250-7005
BACKGROUND: Aberrant methylation of cytosine in promoter CpG islands is a recognized contributory process to carcinogenesis. This study explores the methylation profile of RUNX3 in combination with p16, RASSF1A, CDH1 and hMLH1 in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Genomic DNA was extracted from 19 fresh frozen NPC biopsies, which were then subjected to bisulfite conversion and methylation-specific PCR for analysis of promoter hypermethylation for the five respective genes. Three cell lines, SNU1, RKO and LS174T, were used as controls. RESULTS: The incidences of promoter methylation were as follows: RUNX3 0/19 (0%), p16 6/19 (32%), RASSF1A 13/19 (68%), CDH1 9/19 (47%) and hMLH1 4/19 (21%). Ninety-five percent of the tumor specimens displayed aberrant methylation in at least one of these genes. No significant correlation between methylation status of these genes and clinical parameters was found. CONCLUSION: Methylation of multiple genes is involved in critical pathways for cancer development in NPC. Promoter hypermethylation for RUNX3 was, however, not present.
Dong P, Loh M, Mondry A, 2005, The "impact factor" revisited., Biomed Digit Libr, Vol: 2
The number of scientific journals has become so large that individuals, institutions and institutional libraries cannot completely store their physical content. In order to prioritize the choice of quality information sources, librarians and scientists are in need of reliable decision aids. The "impact factor" (IF) is the most commonly used assessment aid for deciding which journals should receive a scholarly submission or attention from research readership. It is also an often misunderstood tool. This narrative review explains how the IF is calculated, how bias is introduced into the calculation, which questions the IF can or cannot answer, and how different professional groups can benefit from IF use.
Mondry A, Pengbo L, Loh M, et al., 2005, Z-velocity in screening for intrauterine growth restriction., Ultrasound Obstet Gynecol, Vol: 26, Pages: 634-638, ISSN: 0960-7692
OBJECTIVES: Ultrasound scans provide the basis for detection of intrauterine growth restriction (IUGR) but often fail to distinguish IUGR from small-for-gestational age (SGA) fetuses. This study introduces the concept of Z-velocity, calculated as changes in Z-scores over time, as an additional criterion in the diagnosis of IUGR. METHODS: A computer program simulated 50 000 fetal abdominal circumference (FAC) scans based on published growth formulae. False-positive rates were calculated to determine optimal scan time and scan intervals. Using an independent simulation of 32 500 FAC scans, the two methods were compared using receiver-operating characteristics (ROC) curve analysis. RESULTS: ROC showed areas under the curve of > 0.74 over the complete range of scan intervals. The positive predictive value of growth arrest as the only diagnostic criterion was, however, too low to recommend it as an exclusive or the first diagnostic criterion. CONCLUSIONS: Z-velocity can be used to decide whether further investigations for growth abnormality are required in fetuses that fall below the 10(th) percentile. The gain of combined diagnostic approaches should be calculated from large databases that include the neonatal ponderal index as the gold standard.
Dong P, Loh M, Mondry A, 2005, Relevance similarity: an alternative means to monitor information retrieval systems., Biomed Digit Libr, Vol: 2
BACKGROUND: Relevance assessment is a major problem in the evaluation of information retrieval systems. The work presented here introduces a new parameter, "Relevance Similarity", for the measurement of the variation of relevance assessment. In a situation where individual assessment can be compared with a gold standard, this parameter is used to study the effect of such variation on the performance of a medical information retrieval system. In such a setting, Relevance Similarity is the ratio of assessors who rank a given document same as the gold standard over the total number of assessors in the group. METHODS: The study was carried out on a collection of Critically Appraised Topics (CATs). Twelve volunteers were divided into two groups of people according to their domain knowledge. They assessed the relevance of retrieved topics obtained by querying a meta-search engine with ten keywords related to medical science. Their assessments were compared to the gold standard assessment, and Relevance Similarities were calculated as the ratio of positive concordance with the gold standard for each topic. RESULTS: The similarity comparison among groups showed that a higher degree of agreements exists among evaluators with more subject knowledge. The performance of the retrieval system was not significantly different as a result of the variations in relevance assessment in this particular query set. CONCLUSION: In assessment situations where evaluators can be compared to a gold standard, Relevance Similarity provides an alternative evaluation technique to the commonly used kappa scores, which may give paradoxically low scores in highly biased situations such as document repositories containing large quantities of relevant data.
Mondry A, Loh M, Liu P, et al., 2005, Polymorphisms of the insertion / deletion ACE and M235T AGT genes and hypertension: surprising new findings and meta-analysis of data., BMC Nephrol, Vol: 6
BACKGROUND: Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currently most studies focus on the genes coding for proteins that regulate blood pressure as their physiological role makes them prime suspects. The present study examines how polymorphisms of the insertion/deletion (I/D) ACE and M235T AGT genes account for presence and severity of hypertension, and embeds the data in a meta-analysis of relevant studies. METHODS: The I/D polymorphisms of the ACE and M235T polymorphisms of the AGT genes were determined by RFLP (restriction fragment length polymorphism) and restriction analysis in 638 hypertensive patients and 720 normotensive local blood donors in Weisswasser, Germany. Severity of hypertension was estimated by the number of antihypertensive drugs used. RESULTS: No difference was observed in the allele frequencies and genotype distributions of ACE gene polymorphisms between the two groups, whereas AGT TT homozygotes were more frequent in controls (4.6% vs. 2.7%, P = .08). This became significant (p = 0.035) in women only. AGT TT genotype was associated with a 48% decrease in the risk of having hypertension (odds ratio: 0.52; 95% CI, 0.28 to 0.96), and this risk decreased more significantly in women (odds ratio: 0.28; 95% CI, 0.1 to 0.78). The meta-analysis showed a pooled odds ratio for hypertension of 1.21 (TT vs. MM, 95% CI: 1.11 to 1.32) in Caucasians. No correlation was found between severity of hypertension and a specific genotype. CONCLUSION: The ACE I/D polymorphism does not contribute to the presence and severity of essential hypertension, while the AGT M235T TT genotype confers a significantly decreased risk for the development of hypertension in the population studied here. This contrasts to the findings of meta-analyses, whereb
Dong P, Wong LL, Ng S, et al., 2004, Quantitative evaluation of recall and precision of CAT Crawler, a search engine specialized on retrieval of Critically Appraised Topics., BMC Med Inform Decis Mak, Vol: 4
BACKGROUND: Critically Appraised Topics (CATs) are a useful tool that helps physicians to make clinical decisions as the healthcare moves towards the practice of Evidence-Based Medicine (EBM). The fast growing World Wide Web has provided a place for physicians to share their appraised topics online, but an increasing amount of time is needed to find a particular topic within such a rich repository. METHODS: A web-based application, namely the CAT Crawler, was developed by Singapore's Bioinformatics Institute to allow physicians to adequately access available appraised topics on the Internet. A meta-search engine, as the core component of the application, finds relevant topics following keyword input. The primary objective of the work presented here is to evaluate the quantity and quality of search results obtained from the meta-search engine of the CAT Crawler by comparing them with those obtained from two individual CAT search engines. From the CAT libraries at these two sites, all possible keywords were extracted using a keyword extractor. Of those common to both libraries, ten were randomly chosen for evaluation. All ten were submitted to the two search engines individually, and through the meta-search engine of the CAT Crawler. Search results were evaluated for relevance both by medical amateurs and professionals, and the respective recall and precision were calculated. RESULTS: While achieving an identical recall, the meta-search engine showed a precision of 77.26% (+/-14.45) compared to the individual search engines' 52.65% (+/-12.0) (p < 0.001). CONCLUSION: The results demonstrate the validity of the CAT Crawler meta-search engine approach. The improved precision due to inherent filters underlines the practical usefulness of this tool for clinicians.
Mondry A, Zhu A-L, Loh M, et al., 2004, Active collaboration with primary care providers increases specialist referral in chronic renal disease., BMC Nephrol, Vol: 5
BACKGROUND: Late referral to specialist nephrological care is associated with increased morbidity, mortality, and cost. Consequently, nephrologists' associations recommend early referral. The recommendations' effectiveness remains questionable: 22-51% of referrals need renal replacement therapy (RRT) within 3-4 months. This may be due to these recommendations addressing the specialist, rather than the primary care providers (PCP). The potential of specialist intervention aiming at slowing progression of chronic renal failure was introduced individually to some 250 local PCPs, and referral strategies were discussed. To overcome the PCPs' most often expressed fears, every referred patient was asked to report back to his PCP immediately after the initial specialist examination, and new medications were prescribed directly, and thus allotted to the nephrologist's budget. METHODS: In retrospective analysis, the stage of renal disease in patients referred within three months before the introductory round (group A, n = 18), was compared to referrals two years later (group B, n = 50). RESULTS: Relative number of patients remained stable (28%) for mild/ moderate chronic kidney disease (MMCKD), while there was a noticeable shift from patients referred severe chronic kidney disease (SCKD) (group A: 44%, group B: 20%) to patients referred in moderate chronic kidney disease (MCKD) (group A: 28%, group B: 52%). CONCLUSION: Individually addressing PCPs' ignorance and concerns noticeably decreased late referral. This stresses the importance of enhancing the PCPs' problem awareness and knowledge of available resources in order to ensure timely specialist referral.
Tan EC, Loh M, 2004, The Singapore polymorphism/mutation database: Our experience with setting up a country-specific database, Blood and DNA, Editors: Arnason, Nordal, Arnason, Reykjavik, Publisher: University of Iceland Press, Pages: 51-63
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