Pharmacogenetics in type 2 diabetes:Influence on response to oral hypoglycemic agents

Adem Yesuf Dawed, Kaixin Zhou, Ewan Robert Pearson  Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, Scotland, UK Abstract: Type 2 diabetes is one of the leading causes of morbidity and mortality, consuming a significant proportion of public health spending. Oral hypoglycemic agents (OHAs) are the frontline treatment approaches after lifestyle changes. However, huge interindividual variation in response to OHAs results in unnecessary treatment failure. In addition to nongenetic factors, genetic factors are thought to contribute to much of such variability, highlighting the importance of the potential of pharmacogenetics to improve therapeutic outcome. Despite the presence of conflicting results, significant progress has been made in an effort to identify the genetic markers associated with pharmacokinetics, pharmacodynamics, and ultimately therapeutic response and/or adverse outcomes to OHAs. As such, this article presents a comprehensive review of current knowledge on pharmacogenetics of OHAs and provides insights into knowledge gaps and future directions. Keywords: pharmacogenetics, type 2 diabetes, oral hypoglycemic agents, pharmacokinetics, pharmacodynamics, respons

Tuberculosis Lymphadenitis and Human Immunodeficiency Virus Co-infections among Lymphadenitis Patients in Northwest Ethiopia

BACKGROUND: Tuberculosis and human immunodeficiency virus (HIV) are among the major health problems in Ethiopia. This study assessed the proportion of tuberculosis lymphadenitis (TBLN), HIV infection and their co-infection among TBLN presumptive individuals at the selected hospitals in NorthwestEthiopia.METHODS: Institution based cross sectional study was carried out. Data on demographic and clinical variables were collected with standardized questionnaire. Microbiological culture was done on specimen obtained by fine needle aspirates. The HIV status was determined by rapid anti-HIV antibody test. Data was entered and scrutinized using SPSS version 20 statistical packages. A stepwise logistic regression model was used. The result was considered as statistically significant at P<0. 05.RESULTS: A total of 381 lymphadenitis patients were included in the study. The overall prevalence of TBLN and HIV were at 250(65.6%) and 9(2.4%), respectively and their co-infection was at 6(2.4%). Based on the cytological examination, 301(79.0%) of them were diagnosed as TBLN. The age group, (P=0.01) and residency, (P=0.01) were found significantly associated with TBLN. Similarly, unsafe sex was also statistically significant for HIV infection (P=0.007).CONCLUSION: Tuberculosis lymphadenitis is the leading cause of TB and lymphadenitis in the region. However, TBLN-HIV coinfection was promisingly low. High rate of discrepancy was noticed between cytological and culture results. Hence, the TBLN diagnostic criteria shall pursue revision

Drug resistance patterns of bacterial isolates from infected wounds at Bahir Dar Regional Health Research Laboratory Center, Northwest Ethiopia

Background: An increased antibiotic resistance of bacterial isolates from wound infections is a major therapeutic challenge. The aim of this study was to identify bacterial isolates associated with wound infection and to determine their current antimicrobial susceptibility profile.Methods: This is a retrospective cross-sectional study in which we analyzed the records of 380 wound swab culture results that have been processed at Bahir Dar Regional Health Research Laboratory Center in the period of 1 January 2013 to 30 December 2015. Swabs from different wound types were collected aseptically and analyzed using standard bacteriological procedures. Antimicrobial susceptibility testing was performed using disc diffusion technique as per the standard protocol. Demographic and bacteriological data were collected using a data extraction sheet. The data were cleaned, entered and analyzed using SPSS version 22.Results: The overall bacterial isolation rate was at 61.6% (234/380). More than half 123 (52.6%) of the isolates were gram positive and 111 (47.4%) were gram negatives. The predominant isolates were S. aureus at 100 (42.7%) followed by E. coli, 33 (14.1%), P. aeruginosa, 26 (11.1%) and S. pyogenes, at 23 (9.8%). The proportion of multidrug resistant (MDR) bacterial pathogens was at 54.3%. Out of these, 35 (15.1%) of the isolates were resistant to more than five drugs. The highest resistance rate at (85.9%) was documented for ampicillin by gram-negative isolates. Whereas the highest resistance rate among gram positive isolates was against erythromycin (31.1%). The resistance rate of S. aureus for penicillin was at 69.7%.Conclusions: High frequency of mono and multi-drug resistant bacterial pathogens were documented. Thus, an alternative method to the causative agent and antimicrobial susceptibility testing surveillance in areas where there is no culture facility is needed to assist health professionals for the selection of appropriate antibiotics. [Ethiop. J. Health Dev. 2016;30(3):112-117]Keywords: Wound infection, bacterial isolates, and antimicrobial susceptibility profil

Health impacts of bedbug infestation: A case of five towns in Amhara Region, Ethiopia

Background: Bedbug is a wingless human blood-sucking bug that generally infests houses and beds. Bedbug infestation is prevalent across the country. Despite its prevalence, however, there is scarce information on the epidemiological, psychological, social and public health impacts of the infestation. This lack may arise from the absence of sufficient research in the area. The impetus for this study arose from this recognition. This study therefore assessed the extent of bedbug infestation in five towns in Amhara Regional State, Ethiopia, and its impact on public health in the areas considered in this study.Methods: A community-based cross sectional study was conducted in five towns of Amhara Regional State from 1 March 2015 to 30 June 2016. Bedbug inspection was done following the Michigan manual for prevention and control of bedbug recommendation. The presence of a living or dead bedbugs, their eggs, their skin discarded in shedding, and their fecal stains or droppings were taken as an infestation. In addition, data from households were collected using pretested, structured and interviewer-administered questionnaire. The data were analyzed using SPSS version 20. Both bivariate and multivariate logistic regressions were computed to identify associated factors.Results: From the 203 residential institutions surveyed, evidence of prevalence of bedbugs was located in 75.9% (154) houses. From among the infested residents, 87%, 83.1%, and 71.4% had faced one or more psychological, social and health impacts, respectively. Residential institutions in Bahir Dar town administration were 3.4 times more likely to be infested by bedbug than those in Amanuel town (AOR: 3.4; 95% CI: 1-11). The chances that residents of Kobo town administration had to be infested by bedbug were 41 times more than that of the residents in Amanuel town (AOR: 41; 95%CI: 8-206). However, no statistically significant difference was observed between the rates of bedbug infestation and the type of residential institutions.Conclusions: Bedbug infestation was found to be a major public health problem in Bahir Dar, Woreta and Kobo towns. A significant psychological, social and health impact was observed in the communities. Thus, aggressive public health promotion campaigns against bedbug are recommended to empower the communities and equip them with preventive strategies. Moreover, an effective pest management strategy also needs to be made a priority health agenda, in the particular areas of study. A larger study is recommended to assess more in-depth impacts of bedbug infestation on public health [Ethiop. J. Health Dev. 2017;31(4):251-258]Keywords: Bedbug infestation, Ethiopi

Knowledge and practice on magnitude, diagnosis, treatment and prevention strategies of Hepatocellular Carcinoma in Ethiopia: A Systematic Review

Introduction: In Ethiopia, hepatocellular carcinoma (HCC) is the most common cancer with 100% fatality rate. HCC cases in low income countries die within few months following diagnosis. There is lack of information on the burden, risk factors, diagnosis modalities, surveillance strategies and treatment approaches to HCC in Ethiopia.Objective: To analyze the existing evidence related to burden, risk factors, diagnosis modalities, surveillance strategies, and treatment and prevention strategies of HCC in Ethiopia.Methods: All studies done on HCC in Ethiopian irrespective of year of publication and study types were included. Literatures were retrieved from electronic database of PubMedand Cochrane library during September/2016 to January 2/2017. Key words and mesh terms such as ‘hepatocellular carcinoma’, ‘hcc’, ‘hepatoma’, ‘malignant hepatoma’, ‘hepatocarcinoma’ were used to search for documents. Besides, we searched for articles, guidelines and reviews from world health organizations, lancet and Google scholar sites. Each of the retrieved studies was assessed by two authors for inclusion based on the eligibility criteria, and for quality using the critical appraisal checklist. Qualitative data were synthesized for analyzing the theories of studies. Medley reference manager was used to manage citations.Results: A total of 1448 literatures were retrieved. Eight studies fulfill the eligibility criteria, however, only three were full-fledged articles. HCC is clinically characterized by exhaustion, loss of appetite, rapid loss of weight, epigastric pain, right upper abdominal quadrant pain with a rapidly growing mass, jaundice, and ascites with or without hepatomegaly and splenomegaly. Data on HCC proportion among liver disease patients lies between 16.1%-19.2%. Cirrhosis followed by hepatotoxic indigenous drugs and viral hepatitis were found to be as major risk factor for HCC. In Ethiopia, there is no surveillance activity and no standard staging systems. Furthermore, there was no policy frame -work for management of HCC.Conclusion: As compared to other countries, Ethiopia is far behind in addressing HCC. There is no national policy framework and guideline for the management of HCC. Moreover, HCC is a neglected cancer that is considered as a death penalty by the community. Health professionals working in health facilities and health offices should share the data they have to the scientific community and policy makers, for further searching solutions and informed decision, respectively. An intensified public health strategy on health education and early case detection is of critical importance. In addition concerted effort should be made to develop HCC prevention and treatment modality.Key words: Hepatocellular Carcinoma, Ethiopi

Xpert MTB/RIF assay for the diagnosis of Mycobacterium tuberculosis and its Rifampicin resistance at Felege Hiwot and Debre Tabor Hospitals, Northwest Ethiopia: A preliminary implementation research

Background: The World Health Organization endorsed GeneXpert MTB/RIF (Xpert) assay for the diagnosis of tuberculosis (TB) and multidrug resistant tuberculosis (MDR-TB) in 2010. However, the practice of using this novel diagnostic method is still limited in a high TB and human immunodeficiency virus (HIV) burden settings, including Ethiopia. Therefore, we conducted this study aimed at describing the first implementation status of Xpert assay in the diagnosis of TB and MDR-TB at Felege Hiwot Referral Hospital (FHRH) and Debre Tabor General Hospital (DTGH), Northwest Ethiopia.Methods: We analyzed the records of 1922 (FHRH=544 and DTGH=1378) presumptive TB patients diagnosed using Xpert test from 1 November 2015 to 30 April 2016 at FHRH and DTGH, Northwest Ethiopia. All patients who had registered data on their sex, age, HIV status, presumptive MDR-TB status and Xpert results were included for analysis. Data were retrieved directly from GeneXpert result registration log book using data extraction sheet. Data were entered, cleaned, and analyzed using SPSS statistical software package; p < 0.05 was considered to be significant.Results: Overall Xpert assay properly diagnosed 14.6% of the cases (258/1922). Among these, rifampicin (RIF) resistance was detected at 9.3% (24/258). In the studied settings, clinical data showed that 81.0% (1556/1922) of the cases were MDR- TB. Among the study subjects, 888 (46.2 %) of them were HIV positive. However, TB-HIV co-infection rate was at 41.9% (108/258). Of the total patients registered, 1005 (52.3%) of whom were males. The mean age of patients was 31.1 years with SD of 17.5. Significant predictors of the Xpert test were: age (p=0.000), sex (p=0.009), HIV status (p=0.003) and presumptive MDR-TB (p=0.000).Conclusions: In the studied areas, large proportion of clinically TB suspected patients were wrongly diagnosed with MDR-TB. Therefore, the use of Xpert assay in health settings with no culture facility will decrease the unnecessary use of anti-TB drugs and improve rapid TB, and MDR-TB detection and proper management of the cases. [Ethiop. J. Health Dev. 2016;30(2):60-65]Keywords: TB, GeneXpert, MTB/RIF assay, Northwest Ethiopi

BURDEN AND DETERMINANT FACTORS OF ANEMIA AMONG ELEMENTARY SCHOOL CHILDREN IN NORTHWEST ETHIOPIA: A COMPARATIVE CROSS SECTIONAL STUDY

Background: Anemia is an indicator of both poor nutrition and health. In low-income countries like Ethiopia, the prevalence of anemia remains high due to several determinant factors. There is a lack of regular surveillance system to determine the magnitude of anemia among school age children. The aim of this study was to determine the burden and determinant factors of anemia among school children. Materials and Methods: A comparative cross-sectional study was conducted from March 2014 to May 2014 among elementary school children in Northwest Ethiopia. Multi stage and simple random sampling techniques were used to select the schools and the study subjects. Standard questionnaire was employed to assess the socioeconomic status of study participants. Intestinal parasitosis infections and hemoglobin level were determined by formula ether concentration technique and automated hematology analyzer, respectively. Descriptive statistics were used to determine the burden of anemia. Stepwise logistic regression was used to identify the determinants of anemia. Results: Among 2,372 elementary school children, the prevalence of anemia was 7.6% (95 % CI: 7% - 9%). The mean hemoglobin level was 11.6 g/dl ranging from 10 g/dl to 13g/dl. The magnitude of hookworm infection was 530 (22.3%). In multivariate analysis anemia was found associated with residence, source of water, availability of latrine, maternal education, family size and hookworm infection. Conclusion: Anemia still remains as a major public health problem among the school children in the study area. Residence, source of water, availability of latrine, maternal education, family size and hookworm infection are also the major determinant factors for the high prevalence of anemia. Therefore, health education, iron supplement and deworming should be given to school age children

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. METHODS: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. FINDINGS: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. INTERPRETATION: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. FUNDING: Bill & Melinda Gates Foundation