Complex-disease networks of trait-associated single-nucleotide polymorphisms (SNPs) unveiled by information theory

Objective

Thousands of complex-disease single-nucleotide polymorphisms (SNPs) have been discovered in genome-wide association studies (GWAS). However, these intragenic SNPs have not been collectively mined to unveil the genetic architecture between complex clinical traits. The authors hypothesize that biological annotations of host genes of trait-associated SNPs may reveal the biomolecular modularity across complex-disease traits and offer insights for drug repositioning.

Methods

Trait-to-polymorphism (SNPs) associations confirmed in GWAS were used. A novel method to quantify trait–trait similarity anchored in Gene Ontology annotations of human proteins and information theory was developed. The results were then validated with the shortest paths of physical protein interactions between biologically similar traits.

Results

A network was constructed consisting of 280 significant intertrait similarities among 177 disease traits, which covered 1438 well-validated disease-associated SNPs. Thirty-nine percent of intertrait connections were confirmed by curators, and the following additional studies demonstrated the validity of a proportion of the remainder. On a phenotypic trait level, higher Gene Ontology similarity between proteins correlated with smaller ‘shortest distance’ in protein interaction networks of complexly inherited diseases (Spearman p<2.2×10⁻¹⁶). Further, ‘cancer traits’ were similar to one another, as were ‘metabolic syndrome traits’ (Fisher''s exact test p=0.001 and 3.5×10⁻⁷, respectively).

Conclusion

An imputed disease network by information-anchored functional similarity from GWAS trait-associated SNPs is reported. It is also demonstrated that small shortest paths of protein interactions correlate with complex-disease function. Taken together, these findings provide the framework for investigating drug targets with unbiased functional biomolecular networks rather than worn-out single-gene and subjective canonical pathway approaches.     

Incorporating molecular and functional context into the analysis and prioritization of human variants associated with cancer

Background and objective

With recent breakthroughs in high-throughput sequencing, identifying deleterious mutations is one of the key challenges for personalized medicine. At the gene and protein level, it has proven difficult to determine the impact of previously unknown variants. A statistical method has been developed to assess the significance of disease mutation clusters on protein domains by incorporating domain functional annotations to assist in the functional characterization of novel variants.

Methods

Disease mutations aggregated from multiple databases were mapped to domains, and were classified as either cancer- or non-cancer-related. The statistical method for identifying significantly disease-associated domain positions was applied to both sets of mutations and to randomly generated mutation sets for comparison. To leverage the known function of protein domain regions, the method optionally distributes significant scores to associated functional feature positions.

Results

Most disease mutations are localized within protein domains and display a tendency to cluster at individual domain positions. The method identified significant disease mutation hotspots in both the cancer and non-cancer datasets. The domain significance scores (DS-scores) for cancer form a bimodal distribution with hotspots in oncogenes forming a second peak at higher DS-scores than non-cancer, and hotspots in tumor suppressors have scores more similar to non-cancers. In addition, on an independent mutation benchmarking set, the DS-score method identified mutations known to alter protein function with very high precision.

Conclusion

By aggregating mutations with known disease association at the domain level, the method was able to discover domain positions enriched with multiple occurrences of deleterious mutations while incorporating relevant functional annotations. The method can be incorporated into translational bioinformatics tools to characterize rare and novel variants within large-scale sequencing studies.     

Protein-network modeling of prostate cancer gene signatures reveals essential pathways in disease recurrence

Objective

Uncovering the dominant molecular deregulation among the multitude of pathways implicated in aggressive prostate cancer is essential to intelligently developing targeted therapies. Paradoxically, published prostate cancer gene expression signatures of poor prognosis share little overlap and thus do not reveal shared mechanisms. The authors hypothesize that, by analyzing gene signatures with quantitative models of protein–protein interactions, key pathways will be elucidated and shown to be shared.

Design

The authors statistically prioritized common interactors between established cancer genes and genes from each prostate cancer signature of poor prognosis independently via a previously validated single protein analysis of network (SPAN) methodology. Additionally, they computationally identified pathways among the aggregated interactors across signatures and validated them using a similarity metric and patient survival.

Measurement

Using an information-theoretic metric, the authors assessed the mechanistic similarity of the interactor signature. Its prognostic ability was assessed in an independent cohort of 198 patients with high-Gleason prostate cancer using Kaplan–Meier analysis.

Results

Of the 13 prostate cancer signatures that were evaluated, eight interacted significantly with established cancer genes (false discovery rate <5%) and generated a 42-gene interactor signature that showed the highest mechanistic similarity (p<0.0001). Via parameter-free unsupervised classification, the interactor signature dichotomized the independent prostate cancer cohort with a significant survival difference (p=0.009). Interpretation of the network not only recapitulated phosphatidylinositol-3 kinase/NF-κB signaling, but also highlighted less well established relevant pathways such as the Janus kinase 2 cascade.

Conclusions

SPAN methodolgy provides a robust means of abstracting disparate prostate cancer gene expression signatures into clinically useful, prioritized pathways as well as useful mechanistic pathways.     

Identifying disease genes and module biomarkers by differential interactions

Objective

A complex disease is generally caused by the mutation of multiple genes or by the dysfunction of multiple biological processes. Systematic identification of causal disease genes and module biomarkers can provide insights into the mechanisms underlying complex diseases, and help develop efficient therapies or effective drugs.

Materials and Methods

In this paper, we present a novel approach to predict disease genes and identify dysfunctional networks or modules, based on the analysis of differential interactions between disease and control samples, in contrast to the analysis of differential gene or protein expressions widely adopted in existing methods.

Results and Discussion

As an example, we applied our method to the study of three-stage microarray data for gastric cancer. We identified network modules or module biomarkers that include a set of genes related to gastric cancer, implying the predictive power of our method. The results on holdout validation data sets show that our identified module can serve as an effective module biomarker for accurately detecting or diagnosing gastric cancer, thereby validating the efficiency of our method.

Conclusion

We proposed a new approach to detect module biomarkers for diseases, and the results on gastric cancer demonstrated that the differential interactions are useful to detect dysfunctional modules in the molecular interaction network, which in turn can be used as robust module biomarkers.     

Long term clinical outcome and bleeding complications among hospital survivors with acute coronary syndromes

Objective

To examine the 21 month clinical outcome and bleeding complications in hospital survivors with non‐ST segment elevation acute coronary syndromes (NSTEACS) who were discharged with combined clopidogrel and aspirin anti‐thrombotic therapy, and compare with those having ST segment elevation myocardial infarction (STEMI) who were discharged with aspirin alone.

Design

Observational study.

Setting

A large university hospital.

Patients

224 patients were admitted to hospital with either NSTEACS or STEMI, and survived to discharge between 1 October 2001 and 31 December 2002.

Main outcome measures

Cardiovascular death, total death, new myocardial infarction, unstable angina requiring hospitalisation, stroke or transient ischaemic attack, coronary revascularisation; and fatal, life threatening, major and minor bleeding over 21 months after discharge.

Results

Despite having no or small infarct (median maximum creatine kinase 155 v 1295 u/l; p<0.001) and taking more antianginal drugs, patients with NSTEACS had similar rates of cardiovascular death (9.5% v 8.3%; p = NS), new myocardial infarction (9.5% v 6.5%; p = NS) or unstable angina requiring hospitalisation (15.5% v 10.2%; p = NS) when compared with STEMI. Fatal, life threatening or major bleeding were <1% in both groups (p = NS); and minor bleeding occurred in 4.3% NSTEACS and 2.8% STEMI patients respectively (p = NS).

Conclusions

Patients with NSTEACS had a similar and unfavourable long term outcome when compared with STEMI. There was no difference in serious bleeding complications between both groups.     

Effect of methionine loading on pulse wave analysis in elderly volunteers

Objective

To test the hypothesis that an acute increase in plasma homocysteine produced by methionine is associated with an acute increase in pulse wave velocity.

Design

A double blind, cross over, placebo controlled design was used and pulse wave velocity, plasma homocysteine, total cholesterol: high density lipoprotein ratio, plasma triglyceride, oxidised low density lipoprotein cholesterol concentrations, apolipoproteins A1 and B, and C reactive protein were measured between 12.5 and 20 hours after methionine loading or placebo.

Results

Between 12.5 and 20 hours after exposure to a methionine loading test, arterial pulse wave velocity showed no significant difference compared with placebo. At 12 hours after exposure to the methionine loading test, in the presence of a controlled diet, triglyceride concentration significantly increased by 32.6% (p<0.02), cholesterol: high density lipoprotein ratio increased significantly by 22.5% (p<0.05) compared with placebo. Simultaneously, systolic blood pressure increased significantly by 4.9% (p<0.02).

Conclusion

In elderly volunteers, acute hyperhomocysteinaemia induced by methionine loading resulted in no overall significant delayed reduction in peripheral arterial distensibility. A significant deterioration in the lipid profile and increased blood pressure was seen during acute hyperhomocysteinaemia.     

The role of surgery for pancreatic cancer: a 12-year review of patient outcome

Introduction

Pancreatic cancer has a poor prognosis with <5% alive at 5 years, despite active surgical treatment. The study aim was to review patients undergoing pancreatic resection and assess the effect of clinical and pathological parameters on survival.

Patients and methods

All patients who had undergone radical pancreatic surgery, January 1996 to December 2008, were identified from the unit database. Additional information was retrieved from the patient records. The demographic, clinical, and pathological records were recorded using Microsoft Excel. Survival was assessed using Kaplan-Meier and predictors of survival determined by multinominal logistic regression and log rank test.

Results

126 patients were identified from the database. The majority (106) had a Whipple''s procedure, 14 had a distal pancreatectomy and 6 had local periampullary excision. The average age of the Whipple''s group of patients was 61.7 years (± 11.7) with most procedures performed for malignancy (n=100). Survival was worse with adenocarcinoma compared to all other pathologies (p=0.013), while periampullary tumours had a better prognosis compared to other locations (p=0.019). Survival decreased with poorer differentiation (p=0.001), increasing pT (p<0.001) and pN stage (p<0.001). Survival was worse with perineural (p=0.04) or lymphovascular invasion (p=0.05). A microscopic postive resection margin (R1) was associated with a worse survival (p=0.007). Tumour differentiation (p=0.001) and positive nodal status (p<0.001) were found to be independent predictors of mortality.

Conclusion

Tumour differentiation and nodal status are important predictors of outcome. A positive resection margin is associated with a poorer survival.     

Raised cardiac troponin T levels in patients without acute coronary syndrome

Objective

To investigate the frequency, diagnosis and outcome of patients admitted to hospital with acute coronary syndrome (ACS) or other conditions associated with raised levels of cardiac troponin T.

Design

Observational study.

Setting

A large university hospital.

Patients

Consecutive patients admitted over an 8‐week period who had a serum troponin T test as part of their clinical assessment were included. Patients were separated into those with raised (⩾0.01 μg/l) or normal (<0.01 μg/l) troponin T levels, and further categorised into those with or without a diagnosis of ACS.

Main outcome measures

In‐hospital mortality in all patients; and 6‐month hospital re‐admissions and all‐cause mortality in patients without or with ACS and raised levels of troponin T.

Results

Of 1021 patients, 118 patients had no ACS but raised troponin T levels, 195 had ACS with raised troponin T, 80 had ACS with normal troponin T and 628 had no ACS with normal troponin T. Their in‐hospital all‐cause mortalities were 36%, 18%, 0% and 3%, respectively (p<0.001, highest mortality v other groups). 6‐month all‐cause mortality remained higher in patients without ACS and with raised levels of troponin T than in those with ACS and raised troponin T (42% v 29%; p = 0.020).

Conclusions

Patients without ACS but with raised levels of troponin T comprised 38% of all hospitalised patients found to have raised troponin T. These patients had worse in‐hospital and 6‐month outcome than those having ACS with raised levels of troponin T.     

Comparison of a basic and an advanced pharmacotherapy-related clinical decision support system in a hospital care setting in the Netherlands

Objective

To compare the clinical relevance of medication alerts in a basic and in an advanced clinical decision support system (CDSS).

Design

A prospective observational study.

Materials and methods

We collected 4023 medication orders in a hospital for independent evaluation in two pharmacotherapy-related decision support systems. Only the more advanced system considered patient characteristics and laboratory test results in its algorithms. Two pharmacists assessed the clinical relevance of the medication alerts produced. The alert was considered relevant if the pharmacist would undertake action (eg, contact the physician or the nurse). The primary analysis concerned the positive predictive value (PPV) for clinically relevant medication alerts in both systems.

Results

The PPV was significantly higher in the advanced system (5.8% vs 17.0%; p<0.05). Significant differences were found in the alert categories: drug–(drug) interaction (9.9% vs 14.8%; p<0.05), drug–age interaction (2.9% vs 73.3%; p<0.05), and dosing guidance (5.6% vs 16.9%; p<0.05). Including laboratory values and other patient characteristics resulted in a significantly higher PPV for the advanced CDSS compared to the basic medication alerts (12.2% vs 23.3%; p<0.05).

Conclusion

The advanced CDSS produced a higher proportion of clinically relevant medication alerts, but the number of irrelevant alerts remained high. To improve the PPV of the advanced CDSS, the algorithms should be optimized by identifying additional risk modifiers and more data should be made electronically available to improve the performance of the algorithms. Our study illustrates and corroborates the need for cyclic testing of technical improvements in information technology in circumstances representative of daily clinical practice.     

A vector space model approach to identify genetically related diseases

Objective

The relationship between diseases and their causative genes can be complex, especially in the case of polygenic diseases. Further exacerbating the challenges in their study is that many genes may be causally related to multiple diseases. This study explored the relationship between diseases through the adaptation of an approach pioneered in the context of information retrieval: vector space models.

Materials and Methods

A vector space model approach was developed that bridges gene disease knowledge inferred across three knowledge bases: Online Mendelian Inheritance in Man, GenBank, and Medline. The approach was then used to identify potentially related diseases for two target diseases: Alzheimer disease and Prader-Willi Syndrome.

Results

In the case of both Alzheimer Disease and Prader-Willi Syndrome, a set of plausible diseases were identified that may warrant further exploration.

Discussion

This study furthers seminal work by Swanson, et al. that demonstrated the potential for mining literature for putative correlations. Using a vector space modeling approach, information from both biomedical literature and genomic resources (like GenBank) can be combined towards identification of putative correlations of interest. To this end, the relevance of the predicted diseases of interest in this study using the vector space modeling approach were validated based on supporting literature.

Conclusion

The results of this study suggest that a vector space model approach may be a useful means to identify potential relationships between complex diseases, and thereby enable the coordination of gene-based findings across multiple complex diseases.     

Tweeting it off: characteristics of adults who tweet about a weight loss attempt

Objective

The purpose of this study was to describe adults who use Twitter during a weight loss attempt and to compare the positive and negative social influences they experience from their offline friends, online friends, and family members.

Materials and methods

Participants (N=100, 80% female, mean age=37.65, SD=8.42) were recruited from Twitter. They completed a brief survey about their experiences discussing their weight loss attempt with their online and offline friends and provided responses to open-ended questions on the benefits and drawbacks of discussing weight on Twitter, Facebook, and weight-specific social networks.

Results

Participants rated their connections on Twitter and weight loss-specific social networks to be significantly greater sources of positive social influence for their weight loss (F(3)=3.47; p<0.001) and significantly lesser sources of negative social influence (F(3)=40.39 and F(3)=33.68 (both p<0.001)) than their offline friends, family, and Facebook friends. Greater positive social influence from Twitter and Facebook friends was associated with greater weight loss in participants’ most recent weight loss attempt (r=0.30, r=0.32; p<0.01). The most commonly reported benefits of tweeting about weight loss include social support, information, and accountability. The most common drawbacks reported are that interactions were too brief and lacked personal connection.

Discussion

People who discuss their weight loss on Twitter report more social support and less negativity from their Twitter friends than their Facebook friends and in-person relationships.

Conclusions

Online social networks should be explored as a tool for connecting patients who lack weight loss social support from their in-person relationships.     

Secular trends in the medical discharge summary in an acute medical hospital

Background

Although recent research has reported an evolution in the level of medical care, little is known about secular trends in the medical discharge summary.

Methods

The audit evaluated the evolution of discharge summary abstract over a decade in an acute medicine hospital among three successive periods of 1994, 2000, and 2005.

Results

Of the 140 random samples of discharge summaries, significant between‐cohort difference existed in the logarithm transformed length of discharge summary; the median length of discharge summary increased from 11 lines in 1994 to 26 lines in 2005 (p<0.001 corrected for multiple comparison). The closest univariate associations of discharge summary length were positively with the year of hospitalisation, length of stay, length of wordings about discharge plan and duplication of previous discharge summary, and negatively with clinical or planned admission (all p<0.01). In a multiple linear regression analysis, the year of patient admission correlated significantly with the length of discharge summary (p<0.001).

Conclusions

Over the 10 year study period, significant secular trends were seen in the discharge summary length and discharge plan documentation. The causes and implications for these trends deserve further investigation.     

Ethnic variations in the management of patients with acute stroke

Background

There is increasing interest in the management of stroke in ethnic minorities but few studies have considered this issue. This study investigated if differences in acute stroke management exist between a white European and Bangladeshi populations living in London, England.

Methods

All stroke surviving patients discharged over a five year period in a major London teaching hospital based in an ethnically diverse area of inner city London were recruited. Cerebrovascular risk factors, their management, and investigation for acute stroke syndromes were recorded and comparison between white and Bangladeshi cohorts was made. Categorical data were analysed using Fisher''s exact test.

Results

Measurement of cholesterol concentrations are undertaken less often in those from a Bangladeshi background (25%) compared with white Europeans (76%) (p<0.0001). Statin therapy tends to be given less often to Bangladeshis. However, neuroimaging (p<0.05) and echocardiography (p<0.0001) is performed more often in Bangladeshis compared with white Europeans.

Conclusion

There are variations in the management of acute stroke because of ethnicity and these variations could have substantial consequences on secondary rates of cerebrovascular and cardiovascular disease. Whether the reasons for this disparity are attributable to inequity or iniquity of care need to be further investigated perhaps along with the development of ethnicity specific protocols. Overall the management of stroke and its risk factors in either racial group remains lamentable.     

Long term prognosis of heart failure after acute coronary syndromes without ST elevation

Background

Information about long term outcomes of patients with acute coronary syndromes (ACS) who have clinically diagnosed heart failure is scarce.

Methods

In a UK registry, this study evaluated patients with non‐ST elevation ACS, recording treatment, and clinical outcomes for six months. In a subgroup, a four year mortality follow up was performed to estimate the impact of the clinical diagnosis of heart failure on survival.

Results

Of 1046 patients, 139 (13%) had a history of clinically diagnosed heart failure. At discharge, ACE inhibitors were prescribed for 58% and 28%, of those with and without a history of heart failure respectively (p<0.001). Rates of angiography, percutaneous intervention, and coronary artery bypass graft were 17.3% and 29.2% (p = 0.003), 5.0% and 8.4% (p = 0.17), and 5.0% and 7.5% (p = 0.3) for these groups respectively. Death or new myocardial infarction at six months occurred in 22% and 10% (p<0.001) and at four years death occurred in 60% and 20% of these groups respectively (p<0.001). In a multivariate analysis prior heart failure carried an odds ratio of 2.0 (p = 0.001) for death or myocardial infarction at six months and 2.4 (p<0.001) for death over four years. New heart failure was associated with an increased risk of death at six months (20% compared with 5%, p<0.001).

Conclusion

A clinical history of heart failure carries a substantial risk of death in patients admitted with ACS without ST elevation. Nearly 60% of those with prior heart failure are dead after four years. After adjustment for confounding factors, prior heart failure more than doubles the risk compared with those with no history.     

Gender differences in retention and survival on antiretroviral therapy of HIV-1 infected adults in Malawi

Background

There is currently a dearth of knowledge on gender differences in mortality among patients on ART in Africa.

Methods

Using data from the national ART monitoring and evaluation system, a survival analysis of all healthcare workers, teachers, and police/army personnel who accessed ART in Malawi by June, September and December 2006 respectively, was undertaken. Gender differences in survival were analysed using Kaplan-Meier estimates and rate ratios were derived from Poisson regression adjusting for confounding.

Results

4670 ART patients (49.8% female) were followed up for a median of 8.7 months after starting ART. Probability of death was significantly higher for men than women (p<0.001). Controlling for age, WHO clinical stage and occupation, men experienced nearly 2 times the mortality of women RR 1.90 [95% CI: 1.57–2.29]. A higher proportion of men initiated ART in WHO stage 4 (p<0.001).

Conclusion

Among healthcare workers, teachers, police/army personnel, men have higher mortality on ART than women. Possible reasons are unclear but could be biological or because men present for ART at a later clinical stage or have poorer adherence to therapy. Improving early access to ART may reduce mortality, especially among men. A gender difference in adherence to therapy needs further investigation.     

Research and applications: Extracting coordinated patterns of DNA methylation and gene expression in ovarian cancer

Objective

DNA methylation, a regulator of gene expression, plays an important role in diverse biological processes including developmental process, carcinogenesis and aging. In particular, aberrant DNA methylation has been largely observed in several types of cancers. Currently, it is important to extract disease-specific gene sets associated with the regulation of DNA methylation.

Materials and methods

Here we propose a novel approach to find the minimum regulatory units of genes, co-methylated and co-expressed gene pairs (MEGP) that are highly correlated gene pairs between DNA methylation and gene expression showing the co-regulatory relationship. To evaluate whether our method is applicable to extract disease-associated genes, we applied our method to a large-scale dataset from the Cancer Genome Atlas extracting significantly associated MEGP and analyzed their functional correlation.

Results

We observed that many MEGP physically interacted with each other and showed high semantic similarity with gene ontology terms. Furthermore, we performed gene set enrichment tests to identify how they are correlated in a complex biological process. Our MEGP were highly enriched in the biological pathway associated with ovarian cancers.

Conclusions

Our approach is useful for discovering coordinated epigenetic markers associated with specific diseases.     

Full impact of laboratory information system requires direct use by clinical staff: cluster randomized controlled trial

Objective

To evaluate the time to communicate laboratory results to health centers (HCs) between the e-Chasqui web-based information system and the pre-existing paper-based system.

Methods

Cluster randomized controlled trial in 78 HCs in Peru. In the intervention group, 12 HCs had web access to results via e-Chasqui (point-of-care HCs) and forwarded results to 17 peripheral HCs. In the control group, 22 point-of-care HCs received paper results directly and forwarded them to 27 peripheral HCs. Baseline data were collected for 15 months. Post-randomization data were collected for at least 2 years. Comparisons were made between intervention and control groups, stratified by point-of-care versus peripheral HCs.

Results

For point-of-care HCs, the intervention group took less time to receive drug susceptibility tests (DSTs) (median 9 vs 16 days, p<0.001) and culture results (4 vs 8 days, p<0.001) and had a lower proportion of ‘late’ DSTs taking >60 days to arrive (p<0.001) than the control. For peripheral HCs, the intervention group had similar communication times for DST (median 22 vs 19 days, p=0.30) and culture (10 vs 9 days, p=0.10) results, as well as proportion of ‘late’ DSTs (p=0.57) compared with the control.

Conclusions

Only point-of-care HCs with direct access to the e-Chasqui information system had reduced communication times and fewer results with delays of >2 months. Peripheral HCs had no benefits from the system. This suggests that health establishments should have point-of-care access to reap the benefits of electronic laboratory reporting.     

Rheumatoid arthritis patients with active disease and no history of cardiac pathology have higher brain natriuretic peptide (BNP) levels than patients with inactive disease or healthy control subjects

Background

Rheumatoid arthritis (RA) is associated with increased incidence cardiac failure. It is yet unclear how much the increased incidence is secondary to ischaemic damage, or whether inflammatory cytokines might have a direct effect on the myocardium

Objectives

To establish if patients with active rheumatoid arthritis but no history of cardiac disease have higher serum levels of brain natriuretic peptide (BNP), than patients with less active RA, or disease-free controls.

Methods

90 patients with RA and 31 healthy control subjects were recruited. Each was screened to exclude previous history of cardiac disease. RA disease activity was measured using the DAS28 assessment, and other demographic, physical and laboratory tests performed. Serum BNP levels were measured in all subjects.

Results

There was no difference in the age, percentage females or BMI between the RA and control subjects. Median BNP in the RA patients was 80.0 pg/ml (IQR 38.0–132.0) compared with 48.5 (26.0–86.0) in the control subjects (p=0.017). There was a significant correlation between DAS28 and serum BNP in the RA group, r=0.37, p<0.01. RA patients were divided into three groups according to DAS28 scores. Patients with very active disease (DAS28>5.1) had significantly higher BNP levels than patients with moderately active disease (3.2ConclusionRA patients with no history of cardiac disease have higher serum BNP levels than healthy control subjects. RA patients with active RA have higher BNP levels than RA patients with moderately active or inactive disease, raising the possibility of a directly depressive effect of inflammatory cytokines on the myocardium     

Ethnic differences in control of cardiovascular risk factors in patients with type 2 diabetes attending an Inner London diabetes clinic

Background

South Asians have higher risk of diabetic complications compared with white Europeans. The aim of this study was to compare management of cardiovascular risk factors between Bangladeshis and white Europeans.

Methods

A retrospective survey of all diabetic patients attending an Inner London hospital diabetic clinic over one year was undertaken. Data were obtained from the hospital diabetes database: presence of macrovascular (myocardial infarction, angina, stroke, transient ischaemic attack, cardiac intervention) and microvascular disease (neuropathy, retinopathy, and nephropathy), glycated haemoglobin, blood pressure, lipids, smoking, and body mass index (BMI) were all determined.

Results

A total of 1162 white European and 912 Bangladeshi patients with full data available were included in the analyses. The groups were equivalent in age, sex, duration of diabetes. Compared with white Europeans, Bangladeshis had more macrovascular disease (19.5% v 11.9% p<0.01), sight threatening retinopathy (7.2% v 3.8%, p<0.01), and nephropathy (15.3% v 9.1%, p<0.01). In addition, Bangladeshis had significantly more male smokers (28.1% v 22.1%, p<0.01), poorer glycaemic control (mean HbA1c 8.6% v 8.1%, p = 0.039), greater proportion with uncontrolled hypercholesterolaemia (total cholesterol >5.0 mmol/l, 31.6% v 26% p = 0.05), and poorer control of blood pressure (proportion with BP >140/80 mm Hg, 43.2% v 32.1%, p<0.01).

Conclusions

South Asians with type 2 diabetes have poorer glycaemic, blood pressure, and lipid control than white Europeans. The reasons for this are probably multifactorial.     

Research productivity of the medical faculty at the American University of Beirut

Objective

To analyse the quality and quantity of scientific publications of the medical faculty at the American University of Beirut (AUB) during a six year period (1996–2001)

Methods

The study included all faculty members in the medical school of AUB in the year 2001. A Medline search inclusive of the years 1996–2001 was done for each faculty member and a total number of 881 publications was obtained.

Results

The faculty consisted of 203 members. Their average productivity rate (mean (SD)) was 1.24 (1.38) publications/faculty member/year (PFY), with a mean impact factor of 2.69 (4.63). Eighteen per cent of the faculty did not have any publication in the six year study period, and only 20% had two or more publications per year. There was a significantly higher publication rate among newly recruited faculty members (0.93 (1.40) PFY for those appointed before 1990, 1.45 (1.24) PFY for those appointed during 1990–1995, and 1.67 (1.43) for those appointed after 1995, p = 0.007), and among those who are younger in age (p<0.01). Collaboration with international investigators resulted in more original publications than work done only at AUB (65% v 35%, p<0.001), and a higher journal impact factor for the publications (3.20 (3.85) v 1.71 (2.36), p<0.05).

Conclusions

This is one of the first studies that analyse the research productivity of the medical faculty in a university setting in a developing country. It shows a wide variation in the research productivity of the faculty members that seems to be related to individual as well as institutional characteristics. Further analysis is needed to define and characterise these factors.