Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in...Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.展开更多
Objective: Drug resistance is considered one of the main threats for tuberculosis control. Our aim was to identify risk factors for drug resistance in tuberculosis patients in the Northern Portugal. Study Design and M...Objective: Drug resistance is considered one of the main threats for tuberculosis control. Our aim was to identify risk factors for drug resistance in tuberculosis patients in the Northern Portugal. Study Design and Methods: Retrospective case-control study. The medical records and drug susceptibility test data from TB patients diagnosed between 31 March 2009 and 1 April 2010 were examined. We enrolled 119 patients with any drug resistance to first line anti-TB drugs and 238 with drug-susceptible TB, matched by age group. Variables analyzed included: gender, country of origin, employment situation, site of disease, previous treatment, presence of diabetes mellitus, HIV infection, alcohol abuse, intravenous drug use, abuse of other drugs and smoking habits. Multivariate conditional logistic regression was used to identify independent predictors for drug-resistant TB. Results: Diabetes mellitus [adjusted odds ratio (OR): 3.54;95% CI: 1.45 - 8.66], intravenous drug use (OR: 4.77;95% CI: 1.24 - 18.32) and previous TB treatment (OR: 2.48;95% CI: 1.12 - 5.49) were found to be risk factors for drug-resistant disease development. Conclusions: Diabetes mellitus, prior tuberculosis treatment, and intravenous drug use were risk factors for drug-resistant disease. The association between diabetes and drug-resistant TB should be further explored. Identifying clinical predictors of drug resistance can allow prompt identification of patients at risk for drug-resistant TB.展开更多
Background:Multidrug resistant tuberculosis(MDR-TB)is a recognized threat to global eforts to TB control and remains a priority of the National Tuberculosis Programs.Additionally,social determinants and socioeconomic ...Background:Multidrug resistant tuberculosis(MDR-TB)is a recognized threat to global eforts to TB control and remains a priority of the National Tuberculosis Programs.Additionally,social determinants and socioeconomic dep‑rivation have since long been associated with worse health and perceived as important risk factors for TB.This study aimed to analyze the spatial distribution of non-MDR-TB and MDR-TB across parishes of the Lisbon metropolitan area of Portugal and to estimate the association between non-MDR-TB and MDR-TB and socioeconomic deprivation.Methods:In this study,we used hierarchical Bayesian spatial models to analyze the spatial distribution of notifcation of non-MDR-TB and MDR-TB cases for the period from 2000 to 2016 across 127 parishes of the seven municipalities of the Lisbon metropolitan area(Almada,Amadora,Lisboa,Loures,Odivelas,Oeiras,Sintra),using the Portuguese TB Surveillance System(SVIG-TB).In order to characterise the populations,we used the European Deprivation Index for Portugal(EDI-PT)as an indicator of poverty and estimated the association between non-MDR-TB and MDR-TB and socioeconomic deprivation.Results:The notifcation rates per 10,000 population of non-MDR TB ranged from 18.95 to 217.49 notifcations and that of MDR TB ranged from 0.83 to 3.70.We identifed 54 high-risk areas for non-MDR-TB and 13 high-risk areas for MDR-TB.Parishes in the third[relative risk(RR)=1.281,95% credible interval(CrI):1.021-1.606],fourth(RR=1.786,95%CrI:1.420-2.241)and ffth(RR=1.935,95%CrI:1.536-2.438)quintile of socioeconomic deprivation presented higher non-MDR-TB notifcations rates.Parishes in the fourth(RR=2.246,95%CrI:1.374-3.684)and ffth(RR=1.828,95%CrI:1.049-3.155)quintile of socioeconomic deprivation also presented higher MDR-TB notifcations rates.Conclusions:We demonstrated signifcant heterogeneity in the spatial distribution of both non-MDR-TB and MDRTB at the parish level and we found that socioeconomically disadvantaged parishes are disproportionally afected by both non-MDR-TB and MDR-TB.Our fndings suggest that the emergence of MDR-TB and transmission are specifc from each location and often diferent from the non-MDR-TB settings.We identifed priority areas for intervention for a more efcient plan of control and prevention of non-MDR-TB and MDR-TB.展开更多
基金Supported by NIH Fogarty International Center Grant,No.1D43TW008330-01A1Millennium Promise Award,Noncommunicable Chronic Diseases Leadership Training Program,NHLS Research Trust,Division of Nephrology Research Fund,University of the Witwatersrand,Johannesburg and FRC Individual grant,University of the Witwatersrand,Johannesburg
文摘Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.
文摘Objective: Drug resistance is considered one of the main threats for tuberculosis control. Our aim was to identify risk factors for drug resistance in tuberculosis patients in the Northern Portugal. Study Design and Methods: Retrospective case-control study. The medical records and drug susceptibility test data from TB patients diagnosed between 31 March 2009 and 1 April 2010 were examined. We enrolled 119 patients with any drug resistance to first line anti-TB drugs and 238 with drug-susceptible TB, matched by age group. Variables analyzed included: gender, country of origin, employment situation, site of disease, previous treatment, presence of diabetes mellitus, HIV infection, alcohol abuse, intravenous drug use, abuse of other drugs and smoking habits. Multivariate conditional logistic regression was used to identify independent predictors for drug-resistant TB. Results: Diabetes mellitus [adjusted odds ratio (OR): 3.54;95% CI: 1.45 - 8.66], intravenous drug use (OR: 4.77;95% CI: 1.24 - 18.32) and previous TB treatment (OR: 2.48;95% CI: 1.12 - 5.49) were found to be risk factors for drug-resistant disease development. Conclusions: Diabetes mellitus, prior tuberculosis treatment, and intravenous drug use were risk factors for drug-resistant disease. The association between diabetes and drug-resistant TB should be further explored. Identifying clinical predictors of drug resistance can allow prompt identification of patients at risk for drug-resistant TB.
文摘Background:Multidrug resistant tuberculosis(MDR-TB)is a recognized threat to global eforts to TB control and remains a priority of the National Tuberculosis Programs.Additionally,social determinants and socioeconomic dep‑rivation have since long been associated with worse health and perceived as important risk factors for TB.This study aimed to analyze the spatial distribution of non-MDR-TB and MDR-TB across parishes of the Lisbon metropolitan area of Portugal and to estimate the association between non-MDR-TB and MDR-TB and socioeconomic deprivation.Methods:In this study,we used hierarchical Bayesian spatial models to analyze the spatial distribution of notifcation of non-MDR-TB and MDR-TB cases for the period from 2000 to 2016 across 127 parishes of the seven municipalities of the Lisbon metropolitan area(Almada,Amadora,Lisboa,Loures,Odivelas,Oeiras,Sintra),using the Portuguese TB Surveillance System(SVIG-TB).In order to characterise the populations,we used the European Deprivation Index for Portugal(EDI-PT)as an indicator of poverty and estimated the association between non-MDR-TB and MDR-TB and socioeconomic deprivation.Results:The notifcation rates per 10,000 population of non-MDR TB ranged from 18.95 to 217.49 notifcations and that of MDR TB ranged from 0.83 to 3.70.We identifed 54 high-risk areas for non-MDR-TB and 13 high-risk areas for MDR-TB.Parishes in the third[relative risk(RR)=1.281,95% credible interval(CrI):1.021-1.606],fourth(RR=1.786,95%CrI:1.420-2.241)and ffth(RR=1.935,95%CrI:1.536-2.438)quintile of socioeconomic deprivation presented higher non-MDR-TB notifcations rates.Parishes in the fourth(RR=2.246,95%CrI:1.374-3.684)and ffth(RR=1.828,95%CrI:1.049-3.155)quintile of socioeconomic deprivation also presented higher MDR-TB notifcations rates.Conclusions:We demonstrated signifcant heterogeneity in the spatial distribution of both non-MDR-TB and MDRTB at the parish level and we found that socioeconomically disadvantaged parishes are disproportionally afected by both non-MDR-TB and MDR-TB.Our fndings suggest that the emergence of MDR-TB and transmission are specifc from each location and often diferent from the non-MDR-TB settings.We identifed priority areas for intervention for a more efcient plan of control and prevention of non-MDR-TB and MDR-TB.