Nitazoxanide and doxycycline sensitivity among metronidazole resistant helicobacter pylori isolates from patients with gastritis

Background: Antibiotic therapy should be done based on resistance characteristics of Helicobacter pylori strains to commonly prescribed antibiotics in areas with higher resistance rates. Objectives: This study examined antibacterial activity of nitazoxanide and doxycycline against clinical H. pylori isolates showing different metronidazole resistance levels. Methods: A total of 122 patients, who underwent endoscopy were enrolled in this study from 3 hospitals of Tehran, during November 2014 to July 2015. Helicobacter pylori isolates were obtained from gastric biopsies of the patients after culture in specific culture medium and characterization by both biochemical and molecular methods. Antimicrobial susceptibility to metronidazole was detected using the agar dilution method and minimum inhibitory concentrations of nitazoxanide and doxycycline were determined for metronidazole resistant strains. Results: From a total of 122 gastric biopsy specimens, 55 H. pylori strains were recovered (45). Thirty-three of these strains (60.0) were resistance to metronidazole. MIC50 and MIC90 values for metronidazole were 32 and 64 µg/mL, respectively. MIC50 and MIC90 values for doxycycline and nitazoxanide were measured as 4 and �8 µg/mL, and 8 and �32 µg/mL, respectively. Conclusions: Dominance of high level metronidazole resistance H. pylori strains among the studied patients questioned its usefulness for first-line therapy in Iran. Nitazoxanide and doxycycline showed superior activity against H. pylori strains in comparison to metronidazole, which should be considered for alternative therapies. © 2018, Kowsar Medical Publishing Company. All rights reserved

Non-alcoholic steatohepatitis and influence of age and gender on histopathologic findings

AIM: To characterize the histopathologic specifications of non-alcoholic steatohepatitis (NASH) according to age and gender. METHODS: An analytical cross-sectional study was conducted in two private gastroenterology clinics on biopsy proven patients suffering from NASH. Biopsy histopathologic findings as well as demographic and laboratory data of the patients at the time of biopsy were gathered retrospectively from clinical records. The grading and staging of histopathologic findings were performed according to the Brunt method after reevaluation of the slides by a pathologist. Patients were divided into two groups according to age (below and above 55 years). Mean quantitative grade of all pathologic findings were also calculated according to Brunt scoring values. RESULTS: A total number of 77 NASH patients, consisting of 58 males (75.3) and 19 (24.7) females with a mean age of 41.99 ± 11.80 years (range, 18-70 years), were enrolled. The mean age (48.72 ± 13.99 years vs 39.74 ± 10.16 years, P = 0.004) and aspartate aminotransferase level (75.11 ± 29.68 U/L vs 52.78 ± 25.00 U/L, P = 0.002) was significantly higher in female patients. Mean quantitative grade of hepatosteatosis was significantly higher in females (2.00 ± 0.82 vs 1.59 ± 0.68, P = 0.031) compared to males. Fifty four percent (34/65) of young patients had mild hepatosteatosis (Grade I) while only one patient (11.2) in the older group had grade I hepatosteatosis. Patients aged � 55 had significantly more severe hepatosteatosis (Grade III) (44.4 vs 9.5, P = 0.007) and the mean quantitative grade of hepatosteatosis was significantly higher among them (2.33 ± 0.71 vs 1.56 ± 0.67, P = 0.002). Multivariate analysis after omitting the confounding role of age revealed a higher grade of hepatosteatosis in female patients (P = 0.010). CONCLUSION: These findings point toward the possible influence of age in the severity of steatohepatitis, portal and lobar inflammation in patients suffering from NASH while gender independently might contribute to the level of steatohepatitis. © 2010 Baishideng

Nitazoxanide and doxycycline sensitivity among metronidazole resistant helicobacter pylori isolates from patients with gastritis

Background: Antibiotic therapy should be done based on resistance characteristics of Helicobacter pylori strains to commonly prescribed antibiotics in areas with higher resistance rates. Objectives: This study examined antibacterial activity of nitazoxanide and doxycycline against clinical H. pylori isolates showing different metronidazole resistance levels. Methods: A total of 122 patients, who underwent endoscopy were enrolled in this study from 3 hospitals of Tehran, during November 2014 to July 2015. Helicobacter pylori isolates were obtained from gastric biopsies of the patients after culture in specific culture medium and characterization by both biochemical and molecular methods. Antimicrobial susceptibility to metronidazole was detected using the agar dilution method and minimum inhibitory concentrations of nitazoxanide and doxycycline were determined for metronidazole resistant strains. Results: From a total of 122 gastric biopsy specimens, 55 H. pylori strains were recovered (45). Thirty-three of these strains (60.0) were resistance to metronidazole. MIC50 and MIC90 values for metronidazole were 32 and 64 µg/mL, respectively. MIC50 and MIC90 values for doxycycline and nitazoxanide were measured as 4 and �8 µg/mL, and 8 and �32 µg/mL, respectively. Conclusions: Dominance of high level metronidazole resistance H. pylori strains among the studied patients questioned its usefulness for first-line therapy in Iran. Nitazoxanide and doxycycline showed superior activity against H. pylori strains in comparison to metronidazole, which should be considered for alternative therapies. © 2018, Kowsar Medical Publishing Company. All rights reserved

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD, and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such a delineation could not be made due to tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a trans-ethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9,272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40,691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analysed the physico-chemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we identified consistent associations across different ethnicities but also identified population-specific signals. We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids such. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins

Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access Article under the CC BY 4.0 license. Background: Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods: The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings: Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation: Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI. Funding: Bill & Melinda Gates Foundation

Global and regional burden of disease and injury in 2016 arising from occupational exposures : a systematic analysis for the Global Burden of Disease Study 2016

Objectives This study provides an overview of the influence of occupational risk factors on the global burden of disease as estimated by the occupational component of the Global Burden of Disease (GBD) 2016 study. Methods The GBD 2016 study estimated the burden in terms of deaths and disability-adjusted life years (DALYs) arising from the effects of occupational risk factors (carcinogens; asthmagens; particulate matter, gases and fumes (PMGF); secondhand smoke (SHS); noise; ergonomic risk factors for low back pain; risk factors for injury). A population attributable fraction (PAF) approach was used for most risk factors. Results In 2016, globally, an estimated 1.53 (95% uncertainty interval 1.39-1.68) million deaths and 76.1 (66.3-86.3) million DALYs were attributable to the included occupational risk factors, accounting for 2.8% of deaths and 3.2% of DALYs from all causes. Most deaths were attributable to PMGF, carcinogens (particularly asbestos), injury risk factors and SHS. Most DALYs were attributable to injury risk factors and ergonomic exposures. Men and persons 55 years or older were most affected. PAFs ranged from 26.8% for low back pain from ergonomic risk factors and 19.6% for hearing loss from noise to 3.4% for carcinogens. DALYs per capita were highest in Oceania, Southeast Asia and Central sub-Saharan Africa. On a per capita basis, between 1990 and 2016 there was an overall decrease of about 31% in deaths and 25% in DALYs. Conclusions Occupational exposures continue to cause an important health burden worldwide, justifying the need for ongoing prevention and control initiatives

The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990�2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The burden of inflammatory bowel disease (IBD) is rising globally, with substantial variation in levels and trends of disease in different countries and regions. Understanding these geographical differences is crucial for formulating effective strategies for preventing and treating IBD. We report the prevalence, mortality, and overall burden of IBD in 195 countries and territories between 1990 and 2017, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods: We modelled mortality due to IBD using a standard Cause of Death Ensemble model including data mainly from vital registrations. To estimate the non-fatal burden, we used data presented in primary studies, hospital discharges, and claims data, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to ensure consistency between measures. Mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were estimated. All of the estimates were reported as numbers and rates per 100 000 population, with 95 uncertainty intervals (UI). Findings: In 2017, there were 6·8 million (95 UI 6·4�7·3) cases of IBD globally. The age-standardised prevalence rate increased from 79·5 (75·9�83·5) per 100 000 population in 1990 to 84·3 (79·2�89·9) per 100 000 population in 2017. The age-standardised death rate decreased from 0·61 (0·55�0·69) per 100 000 population in 1990 to 0·51 (0·42�0·54) per 100 000 population in 2017. At the GBD regional level, the highest age-standardised prevalence rate in 2017 occurred in high-income North America (422·0 398·7�446·1 per 100 000) and the lowest age-standardised prevalence rates were observed in the Caribbean (6·7 6·3�7·2 per 100 000 population). High Socio-demographic Index (SDI) locations had the highest age-standardised prevalence rate, while low SDI regions had the lowest age-standardised prevalence rate. At the national level, the USA had the highest age-standardised prevalence rate (464·5 438·6�490·9 per 100 000 population), followed by the UK (449·6 420·6�481·6 per 100 000). Vanuatu had the highest age-standardised death rate in 2017 (1·8 0·8�3·2 per 100 000 population) and Singapore had the lowest (0·08 0·06�0·14 per 100 000 population). The total YLDs attributed to IBD almost doubled over the study period, from 0·56 million (0·39�0·77) in 1990 to 1·02 million (0·71�1·38) in 2017. The age-standardised rate of DALYs decreased from 26·5 (21·0�33·0) per 100 000 population in 1990 to 23·2 (19·1�27·8) per 100 000 population in 2017. Interpretation: The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background The burden of inflammatory bowel disease (IBD) is rising globally, with substantial variation in levels and trends of disease in different countries and regions. Understanding these geographical differences is crucial for formulating effective strategies for preventing and treating IBD. We report the prevalence, mortality, and overall burden of IBD in 195 countries and territories between 1990 and 2017, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods We modelled mortality due to IBD using a standard Cause of Death Ensemble model including data mainly from vital registrations. To estimate the non-fatal burden, we used data presented in primary studies, hospital discharges, and claims data, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to ensure consistency between measures. Mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were estimated. All of the estimates were reported as numbers and rates per 100 000 population, with 95% uncertainty intervals (UI). Findings In 2017, there were 6.8 million (95% UI 6.4-7.3) cases of IBD globally. The age-standardised prevalence rate increased from 79.5 (75.9-83.5) per 100 000 population in 1990 to 84.3 (79.2-89.9) per 100 000 population in 2017. The age-standardised death rate decreased from 0.61 (0.55-0.69) per 100 000 population in 1990 to 0.51 (0.42-0.54) per 100 000 population in 2017. At the GBD regional level, the highest age-standardised prevalence rate in 2017 occurred in high-income North America (422.0 [398.7-446.1] per 100 000) and the lowest age-standardised prevalence rates were observed in the Caribbean (6.7 [6.3-7.2] per 100 000 population). High Sociodemographic Index (SDI) locations had the highest age-standardised prevalence rate, while low SDI regions had the lowest age-standardised prevalence rate. At the national level, the USA had the highest age-standardised prevalence rate (464.5 [438.6-490.9] per 100 000 population), followed by the UK (449.6 [420.6-481.6] per 100 000). Vanuatu had the highest age-standardised death rate in 2017 (1.8 [0.8-3.2] per 100 000 population) and Singapore had the lowest (0.08 [0.06-0.14] per 100 000 population). The total YLDs attributed to IBD almost doubled over the study period, from 0.56 million (0.39-0.77) in 1990 to 1.02 million (0.71-1.38) in 2017. The age-standardised rate of DALYs decreased from 26.5 (21.0-33.0) per 100 000 population in 1990 to 23.2 (19.1-27.8) per 100 000 population in 2017. Interpretation The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe